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La duplicación en el brazo largo del cromosoma 10 (10q) es una cromosomopatía poco frecuente caracterizada clínicamente por retraso en el crecimiento prenatal y postnatal asociado a hipotonía, retraso en el desarrollo y hallazgos faciales específicos; que representa un reto diagnóstico en el ámbito clínico. Se presenta el caso de una recién nacida remitida para valoración multidisciplinara al Hospital Universitario San Ignacio en Bogotá, Colombia; en quien se documentó al momento del nacimiento fisura de labio y paladar, hipertelorismo, pabellón auricular con implantación baja e hipertrofia de labios menores. Se realizó resonancia magnética cerebral, la cual reportó pequeños quistes connatales adyacentes a las astas frontales de los ventrículos laterales, sin significado patológico, aparente malrotación de ambos hipocampos, hipertelorismo y queilopalatosquisis bilateral. El reporte del cariotipo con bandeo G confirmó complemento cromosómico 46,XX,dup(10)(q23q24); siendo el primer caso reportado en Colombia.
Duplication on the long arm of chromosome 10 (10q) is a rare chromosomopathy characterized clinically by delayed prenatal and postnatal growth associated with hypotonia, delayed development, and specific facial findings, which represents a diagnostic challenge in the clinical setting. We present the case of a newborn referred for multidisciplinary evaluation at the Hospital Universitario San Ignacio in Bogotá, Colombia; in whom cleft lip and palate, hypertelorism, low-set auricle and hypertrophy of the labia minora were documented at birth. Magnetic resonance imaging of the brain was performed, which reported small connatal cysts adjacent to the frontal horns of the lateral ventricles, without pathological significance, apparent malrotation of both hippocampi, hypertelorism, and bilateral cheilopalatoschisis. The G-band karyotype report confirmed chromosomal complement 46, XX, dup (10) (q23q24); being the first reported case in Colombia.
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Humans , Female , Infant, Newborn , Congenital AbnormalitiesABSTRACT
The purpose of our study is to investigate the prognostic value of phosphatase and tensin homolog on chromosome 10 (PTEN) expression in patients with de novo metastatic castration naïve prostate cancer (mCNPC). A total of 205 patients with mCNPC at Fudan University Shanghai Cancer Center (Shanghai, China) were retrospectively examined. Immunohistochemical staining of PTEN was performed on prostate biopsy samples of these patients. Associations among clinicopathological features, patient survival and PTEN protein expression were analyzed. PTEN loss occurred in 58 of 205 (28.3%) patients. Loss of PTEN was significantly correlated with high metastatic volume (P = 0.017). No association between PTEN expression and Gleason score was observed. Patients with PTEN loss had significantly shorter progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001) compared with patients with intact PTEN expression. Multivariate analysis showed that elevated alkaline phosphatase, high metastatic volume and PTEN loss were independent poor prognostic factors for PFS. The Eastern Cooperative Oncology Group performance status (ECOG PS)#8805; 2 and PTEN loss were independent poor prognostic factors for OS. The adjusted hazard ratio of PTEN loss for PFS and OS was 1.67 (95% confidence interval [CI]: 1.14-2.43, P = 0.008) and 1.95 (95% CI: 1.23-3.10, P = 0.005), respectively. PTEN loss was also significantly associated with shorter PFS (P = 0.025) and OS (P < 0.001) in patients with low-volume metastatic disease. Our data showed that PTEN loss is an independent predictor for shorter PFS and OS in patients with de novo mCNPC.
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Humans , Male , China/epidemiology , PTEN Phosphohydrolase/genetics , Prognosis , Prostatic Neoplasms , Retrospective StudiesABSTRACT
Objective:To investigate the molecular mechanism of Qiyu Sanlong prescription （QYSL） in inhibiting the "addiction" of lung cancer A549 cells to miRNA21. Method:The human lung cancer A549 cells were routinely passaged and divided into the blank group， blank serum group， QYSL-containing serum group， and siRNA group. The prepared QYSL-containing serum was used for intervention， with the optimal concentration and action time determined in previous studies. The protein and mRNA expression levels of miRNA21 and related molecules in its target phosphatase and tensin homolog deleted on chromosome 10 （PTEN）/phosphatidylinositol 3-kinase （PI3K） signaling pathway were detected by real-time polymerase chain reaction （Real-time PCR） and Western blot assay. Result:The comparison with the blank serum group revealed that the mRNA expression levels of miRNA21 in the QYSL-containing serum group and the siRNA group were decreased， while the PTEN mRNA expression in the QYSL-containing serum group was increased， showing significant differences （<italic>P</italic><0.01）. Compared with the blank serum， the QYSL-containing serum and siRNA significantly down-regulated PI3K and mammalian target of rapamycin （mTOR） mRNA expression （<italic>P</italic><0.01）， whereas the QYSL-containing serum did not change the mRNA expression of protein kinase B （Akt）. The protein expression levels of PTEN in the QYSL-containing serum group and the siRNA group were obviously elevated in contrast to that in the blank serum group （<italic>P</italic><0.05）. Meanwhile， the protein expression levels of phosphorylated Akt （p-Akt） and phosphorylated mTOR （p-mTOR） evidently declined in the QYSL-containing serum group （<italic>P</italic><0.05）， but there was no significant reduction in total Akt and mTOR protein expression. The PI3K protein expression was slightly down-regulated， with no statistical significance. Conclusion:QYSL inhibits the transcription of miRNA21， increases the expression of PTEN， and reduces the expression of key molecules in PI3K/Akt/mTOR signaling pathway， thus mildly inhibiting the "addiction" of lung cancer cells to oncogenes and blocking their proliferation.
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INTRODUCCIÓN: La hipoplasia de timo es una entidad que puede asociarse a múltiples patologías fetales de ahí la importancia de su diagnóstico y su manejo. OBJETIVO: Utilidad y métodos de evaluación del timo en la ecografía morfológica y valor de la interpretación del análisis genético de los microarrays. CASO CLÍNICO: Se presenta el caso clínico de una gestante en la que se detecta una glándula tímica hipoplásica utilizando para su medición el índice timo-torácico en un plano de tres vasos. Ante estos hallazgos se realiza una amniocentesis para análisis genético usando la QF-PCR y un análisis ARRAY-CGH. RESULTADOS: En el análisis de ARRAY-CGH se observa una duplicación patológica en mosaico compatible con una trisomía del cromosoma 10, alteración genética infrecuente de la que se han reportado unos 50 casos en recién nacidos vivos. Esta alteración presenta un rango muy amplio de alteraciones, desde malformaciones graves a niños completamente normales. En los controles posteriores la gestación es normoevolutiva y finaliza en la semana 40 mediante un parto eutócico de inicio espontáneo naciendo un bebé fenotípicamente normal con un timo de menor tamaño del habitual siendo pronto para saber las consecuencias de esta alteración en su inmunidad. CONCLUSIONES: Por un lado, el timo es una estructura fácil de visualizar en la ecografía morfológica de la semana 20 y su medición mediante el índice timo-torácico nos aporta información útil acerca de posibles patologías fetales. Por otro, tener en cuenta que debemos ser muy cautelosos con la interpretación de resultados de pruebas genéticas cuando éstas no tienen un significado clínico claro.
INTRODUCTION : Thymus hypoplasia can associate many different pathologies so is highly important the diagnosis and the management. OBJECTIVE: Utility and methods in the evaluation of the fetal thymus in the morphological ultrasound and interpretation of microarray results. CLINICAL CASE: We present a case of fetal hypoplastic thymus gland in a pregnant woman. We measure it using the thymus-torax index in a three vessel view. A genetical analysis was made using QF-PCR and Array-CGH. RESULTS: In the ARRAY-CGH analysis it is found a pathological mosaicism that match with chromosome 10 trisomy, a very uncommon genetical alteration with only 50 reported cases. This trisomy can traduce from serious malformations to complete normal children. The parents decide to continue with the pregnancy and in week 40 it finishes with an uncomplicated delivery of a healthy child. In the newborn pediatrics remark a thymus gland smaller than expected but it is early to say if it will have or not consequences in its immunity. CONCLUSION: On one hand the thymus is a structure that we can easily display in the morphological ultrasound in the 20 week of pregnancy and its measure, using the thymus-torax index, can be very helpful in the detection of fetal pathologies. On the other hand, is important being careful when we interpret a genetical alteration without a clear clinical significance.
Subject(s)
Humans , Female , Pregnancy , Infant, Newborn , Thymus Gland/abnormalities , Thymus Gland/diagnostic imaging , Trisomy/genetics , Trisomy/diagnosis , Chromosomes, Human, Pair 10 , Polymerase Chain Reaction/methods , Ultrasonography, Prenatal , Chromosome Aberrations , Microarray Analysis , AmniocentesisABSTRACT
Objective To study the effect of cyclophosphamide(CP) and its metabolites acrolein(ACR) on PTEN gene deleted on chromosome 10 after acting on ovarian cancer cellsSKOV3.Methods Different concentrations of CP and ACR were selected to act on recombinant PTEN protein.The phosphorylation activity of PTEN was detected by PNPP.The expression of PTEN protein was detected by Western blot.The binding mode of drug with protein was detected by the biotin combined with protein;meanwhile the expression change of P53/TP53 in PTEN gene pathway was analyzed.The target protein was obtained by immunoprecipitation(IP) after different drug concentrations acting on the cells.The phosphorylation activity of the target protein was detected by high performance liquid chromatography(HPLC).Results After the drug metabolites acting on recombinant PTEN protein,the phosphorylation activity was decreased with the increase of drug concentration,while the expression of ACR antibody action was increased with the drug concentration elevation.The expression of protein and biotin in different experimental groups was increased with the increase of drug concentration.The PTEN phosphorylation activity was decreased with the drug concentration increased in cells,and so did the expression of TP53 protein.Conclusion CP metabolite ACR induces the cytotoxicity by inhibiting PTEN protein phosphorylation activity.
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Objective To study the effect of simvastatin on the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and β-catenin in myocardial cells of rabbits with chronic heart failure (CHF).Methods Twenty-four male New Zealand rabbits were randomly divided into control group,CHF model group and simvastatin treatment group,with 8 rabbits in each group.The rabbits in CHF model group and simvastatin treatment group were injected with adriamycin (2.0 mg · kg-1) ria ear rein once a week for six weeks,and from the seventh week were injected with adriamycin (1.5 mg · kg-1)once a week for another six weeks to establish the CHF model;the rabbits in control group were injected with the same volume saline.The rabbits in simvastatin treatment group were given simvastatin (1.5 mg · kg-1 · d-1) by intragastric administration at the time point of first injection of adriamycin for 12 weeks;the rabbits in CHF model group and control group were given the same volume saline for 12 weeks.The left ventricular structure and function were determined by color doppler uhrasonography after the modeling.Then the rabbits were sacrificed and the left ventricular walls were taken to observe the changes of myocardial cell structures by hematoxylin-eosin staining.The positive expression rate of PTEN and β-catenin protein was calculated by immunohistochemistry staining.The expression of PTEN and β-catenin mRNA was detected real-time quantitative polymerase chain reaction.Results Compared with the control group,the left ventricular end-systolic dimension (LVESD),left ventricular end-diastolic dimension(LVEDD) were increased and the left ventricular ejection fraction(LVEF) was decreased in the CHF model group and simvastatin treatment group(P ＜ 0.05).Compared with the CHF model group,the LVESD,LVEDD were decreased and the LVEF was increased in the simvastatin treatment group(P ＜ 0.05).The positive expression rate of PTEN protein in myocardial cells of rabbits in control group,CHF model group and simvastatin treatment group was (16.36 ± 0.54) ％,(41.63 + 0.72) ％ and (24.17 ± 0.51) ％ respectively;the positive expression rate of β-catenin protein in myocardial cells of rabbits in control group,CHF model group and simvastatin treatment group was (21.73 ± 0.46)％,(52.26 ±+ 0.72) ％ and (38.42 + 0.56) ％ respectively.The positive expression rates of PTEN and β-catenin protein in myocardial cells of rabbits in CHF model group and simvastatin treatment group were significanlty higher than those in the control group(P ＜ 0.05);the positive expression rates of PTEN and β-catenin protein of myocardial cell in simvastatin treatment group were significantly lower than those in the CHF model group (P ＜ 0.05).The epression of PTEN mRNA and β-catenin mRNA in myocardial cells of rabbits in control group,CHF model group and simvastatin treatment group was 1.91 ± 0.30,4.61 ± 0.71,3.49 ± 0.64 and 1.51 ± 0.21,2.48 ± 0.34,1.51 ±+ 0.25.The expression of PTEN and β-catenin mRNA in myocardial cells of rabbits in CHF model group and simvastatin treatment group were significanlty higher than those in the control group (P ＜ 0.05);the expression of PTEN and β-catenin mRNA in myocardial cells of rabbits in simvastatin treatment group were significantly lower than those in the CHF model group (P ＜ 0.05).Conclusion Simvastatin can inhibit myocardial apoptosis,improve cardiac function of CHF rabbits.It may be related to inhibiting the expression of PTEN and β-catenin.
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Background and purpose:Loss of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is one of the most common somatic genetic aberrations in prostate cancer in Western countries and is frequently associated with tumor progression and poor prognosis. This study aimed to investigate the frequency of PTEN protein loss in Chinese prostate cancer patients and to determine its association with the biochemical recurrence of prostate cancer.Methods:The data from 225 diagnosed localized prostate cancer patients with radical prostatectomy from 2006 to 2011 were collected retrospectively, including patient’s age at diagnosis, prostate-speciifc antigen (PSA) level at diagnosis, Gleason score, clinical stage, surgical margin, and time to biochemical recurrence or not. This study performed PTEN protein immunohistochemistry on tissue microarrays, which were made from 225 Chinese prostate cancer patients mentioned above, treated by radical prostatectomy with one case including 2 cancer spots and 2 adjacent normal gland spots. Correlations of PTEN loss with clinicopathological features were analyzed usingχ2 test. Kaplan-Meier survival model and Cox proportional hazards regression model were used to evaluate the predictive role of PTEN protein expression and patient characteristics for biochemical recurrence. Results:PTEN protein loss was observed in 15% of the patients and was associated with increased preoperative PSA levels (P=0.03) and old age (P=0.009). In univariate Kaplan–Meier analysis, the factors associated with the biochemical recurrence of prostate cancer included PSA levels (P=0.000 4), Gleason sum (P=0.019 8), and PTEN status (P=0.013 1). In multivariable Cox regression analysis, PTEN expression (HR=0.536, P=0.044), PSA levels (HR=1.879, P=0.001), and Gleason score (HR=1.361,P=0.03) were signiifcant in predicting biochemical recurrence of prostate cancer.Conclusion:PTEN protein loss is associated with an increased risk of recurrence, independent of known clinicopathological factors.
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We herein report an analysis of a female baby with a de novo dup(10p)/del(10q) chromosomal aberration. A prenatal cytogenetic analysis was performed owing to abnormal ultrasound findings including a choroid plexus cyst, prominent cisterna magna, and a slightly medially displaced stomach. The fetal karyotype showed additional material attached to the terminal region of chromosome 10q. Parental karyotypes were both normal. At birth, the baby showed hypotonia, upslanting palpebral fissures, a nodular back mass, respiratory distress, neonatal jaundice and a suspicious polycystic kidney. We ascertained that the karyotype of the baby was 46,XX,der(10)(pter-->q26.3::p11.2-->pter) by cytogenetic and molecular cytogenetic analyses including high resolution GTG- and RBG-banding, fluorescence in situ hybridization, comparative genomic hybridization, and short tandem repeat marker analyses. While almost all reported cases of 10p duplication originated from one of the parents with a pericentric inversion, our case is extraordinarily rare as the de novo dup(10p)/del(10q) presumably originated from a rearrangement at the premeiotic stage of the parental germ cell or from parental germline mosaicism.
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Female , Humans , Infant, Newborn , Choroid Plexus , Chromosome Aberrations , Chromosomes, Human, Pair 10 , Cisterna Magna , Comparative Genomic Hybridization , Cytogenetic Analysis , Cytogenetics , Fluorescence , Germ Cells , In Situ Hybridization , Jaundice, Neonatal , Karyotype , Korea , Microsatellite Repeats , Mosaicism , Muscle Hypotonia , Parents , Parturition , Polycystic Kidney Diseases , Stomach , UltrasonographyABSTRACT
Objective To analyse the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in ovarian epithelial cancer and to investigate the relationship between PTEN and clinical pathology and prognosis of ovarian epithelial cancer.Methods Expression of PTEN in 10 normal ovarian tissues,20 benign tumors and 60 cases of ovarian epithelial cancers were detected by immunohistochemical method.Results The positive expression of PTEN in normal ovarian and benign tumor tissues were significantly higher than that in ovarian epithelial cancers (100％ (10/10) vs 80.0％ (16/20) vs 53.3％ (32/60),x2 =7.778 and 4.444 respectively,P ＜ 0.05).The expression of PTEN was correlated to clinical stage,histilogical grade,presence and metastasis of lymph node (x2 =4.339;6.465 ;3.896;10.452;P ＜0.01),but there was no correlation to age,histological type and ascites (x2 =0.004 ;0.388 ; 1.057 ; P ＞ 0.05).Conclusion The expression of PTEN is related to ovarian carcinogenesis and development and may has great value in clinical diagnosis and prognosis of ovarian carcinogenesis.
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Background and purpose: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene is a kind of tumor suppressors, which has been reported to be underexpressed in endometrial carcinoma (EC) tissues by several reports. However, the biological effects and possible mechanisms of PTEN on EC have been known less. In this study, we tried to investigate the effects and possible mechanisms of PTEN on the invasion and migration of endometrial carcinoma cells and to provide a potential target for endometrial carcinoma therapy. Methods:The recombinant plasmid pIRES2-ZsGreen1-PTEN was rebuilt by gene recombination technology;The plasmid was transferred into HEC-1B cells and the cells transfected with pIRES2-ZsGreen1 plasmid were used as control;The expression of PTEN was observed by fluorescence microscope and Western blot assay;Cell migration and invasion was determined by the wound healing assay, transwell migration and invasion assays respectively;The Western blot analysis was performed to detect the expression of ATP-dependent tyrosine kinase (AKT), phosphorylated-AKT (p-AKT) and matrix metalloproteinase-2 (MMP-2). Results:The agarose gel electrophoresis showed a stripe of 1.2 kb which was same to PTEN cDNA;The sequence analysis showed the PCR products owned the same sequence with the coding region of PTEN cDNA in GenBank, suggesting the recombinant plasmid was constructed successfully;The green light of cells observed by fluorescence microscope and the Western blot analysis showed the expression of PTEN was upregulated in the cells transfected with the recombinant plasmid, suggesting the plasmid expressed successfully in HEC-1B cells;The wound healing assay as well as transwell migration assay showed ectopic expression of PTEN suppressed cell migration;The invasive capacity of HEC-1B cells was significantly decreased upon transfection with PTEN plasmid compared to control and untreated groups;Moreover, compared with the control groups, the expression of p-AKT and MMP-2 was downregulated, while there was no significant alteration of the expression of AKT. Conclusion:PTEN could suppress cell migratory and invasive ability of endometrial carcinoma cells by suppressing the phosphorylation of AKT followed by the decrease of MMP-2.
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Objective To investigate the mechanisms of neuroprotective roles of phosphatase and tensin homolog allele activity deleted in chromosome 10 (PTEN) inhibition on neuronal apoptosis after hypoxia-ischemia (HI)damage.Methods The cerebral cortical neurons of newbom Sprague-Dawley rats were cultured in vitro.Oxygen and glucose deprivation (OGD) model was established to imitate HI environment in vivo.Neurons were divided randomly into 3 groups:control group:neurons were treated with normal medium ; OGD group:neurons were treated with OGD for 3 h followed by reperfusion at 0.5,3.0,6.0,12.0,24.0,48.0 h ; PTEN inhibition group:before OGD treatment,neurons were pretreated with PTEN inhibitor,and then the neurons were collected at 24 h after reperfusion.Terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling staining was used to detect the apoptotic cells.Western blot was used to detect the expression of PTEN,p-PTEN,protein kinase B(Akt),p-Akt,synthesis of glucose kinase-3 betal (GSK-3β),p-GSK-3β and myeloid cell ceukemia-1 (Mcl-1).Results 1.As compared with control group,TUNEL positive cells increased after OGD observed by TUNEL staining (P ＜ 0.05).The expression of PTEN was increased,the expressions of p-PTEN,p-Akt,p-GSK-3 β,and Mcl-1 were significantly decreased after OGD (all P ＜ 0.05).However,Akt and GSK-3β remained unchanged at different time points after OGD(all P ＞ 0.05).2.As compared with OGD group,TUNEL positive cells were obviously reduced at 24 h after OGD in PTEN group (P ＜ 0.05).Although total PTEN,Akt,and GSK-3 β were not obviously changed in PTEN group(all P ＞ 0.05),the expressions of p-PTEN,p-Akt,p-GSK-3β,and Mcl-1 were significantly increased after OGD (all P ＜ 0.05).Conclusions HI can induce neuronal apoptosis,and the mechanisms of apoptosis may involve PTEN/Akt/GSK-3β/Mcl-1 pathway.The phosphorylation of Akt and GSK-3β can be increased via PTEN activity inhibition,while the ubiquitination of Mcl-1 would be decreased,and thus reduce the neuronal apoptosis.
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The faded mouse is a coat color mutant that shows faded coat color and age-related loss of pigmentation. This mutation is transmitted by an autosomal recessive gene with 100% penetrance. In the present study, we carried out linkage analysis of the faded (fe) gene using intra-specific backcross panels. Affected faded mice were carefully confirmed by their faded coat color at about 4 weeks of age. In the intra-specific backcross between faded and CBA mice (n=198), the fe gene was mapped to a region 2.1 cM distal to D10mit191. Therefore, the gene order was defined as follows: centromere-D10mit51 (12.4+/-2.4 cM)-D10mit191 (2.1+/-1.0 cM)-fe-D10mit44 (13.3+/-2.4 cM)-D10mit42 (14.4+/-2.5 cM). This linkage map of the fe locus will provide a good entry point to isolate the fe gene. Since the faded mouse has pigmentary abnormalities, this mutant may be a useful model for studies of pigmentary abnormalities in humans.
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Animals , Humans , Mice , Chromosomes, Human, Pair 10 , Gene Order , Genes, Recessive , Mice, Inbred CBA , Penetrance , PigmentationABSTRACT
Recently,phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is suggested as a new agent in the fighting against fibrogenesis.In tumor,DJ-1 is identified as a negative regulator of PTEN.But the expression of DJ-1 and the regulation of PTEN in fibrosis are unclear.Renal fibrosis was induced in 5/6 subtotal nephrectomy rat model.Human proximal tubular epithelial cells (HKC) were treated with transforming growth factor-beta 1 (TGF-β1),or transfected with DJ-1 or PTEN.Confocal microscope was used to investigate the localization of DJ-1 and PTEN.The selective phosphoinositide-3 kinase (PI3K) inhibitor,LY294002,was administered to inhibit PI3K pathway.The DJ-1 and PTEN expression,markers of epithelial-mesenchymal transition (EMT) and Akt phosphorylation were measured by RT-PCR,Western blotting or immunocytochemistry.In vitro,after HKC cells were stimulated with 10 ng/mL TGF-β1 for 72 h,the expression of DJ-1 was increased,and that of PTEN was decreased.In vivo,the same results were identified in 5/6-nephrectomized rats.In normal HKC cells,most of DJ-1 protein localized in cytoplasm,and little in nucleus.TGF-β1 upregulated DJ-1 expression in both cytoplasma and nuclei.In contrary,TGF-β1 emptied cytoplasmic PTEN protein into nucleus.Overexpression of D J-1 decreased the expression of PTEN,promoted the activation of Akt and the expression of vimentin,and also led to the loss of cytoplasmic PTEN.Contrarily,overexpression of PTEN protected HKC cells from TGF-β1-induced EMT.In conclusion,DJ-1 is upregulated in renal fibrosis and DJ-1 mediates EMT by suppressing cytoplasmic PTEN expression and Akt activation.
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PURPOSE: We investigated the effects of phosphatase and tensin homologue deleted on chromosome 10 gene phosphatase and tensin homologue deleted on chromosome 10 gene (PTEN) expression on the cell proliferation and on the responsiveness of troglitazone in osteosarcoma cells. MATERIALS AND METHODS: Western blotting alnalysis was performed to detect the expression of PTEN in U-2OS cells treated with troglitazone. WST (water-soluble tetrazolium) assay was used to evaluate cell proliferation. Flow cytometry was used to determine cell apoptosis. Further, transfection of wild-type PTEN plasmid DNA was used to upregulate PTEN expression. RESULTS: Troglitazone treatment induced growth inhibition of U2-OS cells in a dose- and time-dependent manner. Troglitazone increased the expression of PTEN in a dose-dependent manner. PTEN upregulation induced by troglitazone treatment resulted in cell growth inhibition and apoptosis in U-2OS cells. PTEN over-expression by plasmid transfection enhanced these effects of troglitazone. Moreover, no changes were observed in the mutant type-PTEN group. CONCLUSION: Upregulation of PTEN is involved in the inhibition of cell growth and induction of cell apoptosis by troglitazone. Further, PTEN over-expression can cause cell growth inhibition in osteosarcoma cells and these cell growth inhibitions could be enhance by troglitazone treatment.
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Humans , Apoptosis , Blotting, Western , Cell Proliferation , Chromans , Chromosomes, Human, Pair 10 , DNA , Flow Cytometry , Microfilament Proteins , Osteosarcoma , Plasmids , Thiazolidinediones , Transfection , Up-RegulationABSTRACT
Phosphatase and tensin homologue deleted on chromosome 10(PTEN) is a tumor suppressor which can inhibit proliferation and migration and control apoptosis in a number of cell types,mainly through inhibiting the phosphoinositide 3-kinase(PI3K) signaling pathway.A number of in vitro and in vivo studies has been instrumental in uncovering a direct correlation between deregulated PTEN/PI3K signaling and changes in neuronal morphogenesis,which is likely to have profound bearings upon the pathogenesis of neurological symptoms.This review outlines recent work on the function of PTEN during the formation and maintenance of neuronal circuits in the brain.
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PURPOSE: PTEN and DMBT1, candidate tumor suppressor genes on chromosome 10q, were identified based on deletions in glioblastoma and medulloblastoma cell lines. We examined the occurrences and frequencies of allelic deletions on chromosome 10q23 and 10q25 by loss of heterozygosity (LOH) analysis in 24 pediatric brain tumors to investigate the possible involvement of PTEN and DMBT1 gene deletions in the development of pediatric brain tumors. METHOD: LOH was analyzed by polymerase chain reaction (PCR) of PTEN locus on 10q23 using 2 microsatellite markers, D10S608 and D10S579, and of DMBT1 locus on 10q25-q26.1 using a microsatellite marker, D10S587, in 24 pediatric brain tumor (18 medulloblastomas, 3 ependymomas, 2 glioblastomas and 1 supratentorial primitive neuroectodermal tumor) DNAs extracted from archival tissue specimens (case 1-15, 19) or fresh frozen tissue specimens (case 16-18, 20-24). RESULTS: Allelic deletions were detected in 4 of 23 informative cases (17%) on D10S608, 6 of 24 informative cases (25%) on D10S579, and 8 of 24 informative cases (33%) on D10S587. Overall 11 of 24 cases (46%) showed LOH on chromosome 10q at PTEN or DMBT1 loci, and they were 10 medulloblastomas and 1 ependymoma pathologically. Of 18 medulloblastomas, 7 (39%) exhibited LOH at PTEN locus, 8 (44%) exhibited LOH at DMBT1 locus, and 10 (56%) exhibited LOH at one or both of loci. CONCLUSION: Our results support the notion that PTEN and DMBT1 tumor suppressor gene deletions may be involved in the pathogenesis of pediatric brain tumors. Our results also suggested that PTEN and DMBT1 tumor suppressor gene deletions may not be important in molecular mechanism of glioblastoma development in children as in adults.
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Adult , Child , Humans , Brain Neoplasms , Brain , Cell Line , DNA , Ependymoma , Gene Deletion , Genes, Tumor Suppressor , Glioblastoma , Loss of Heterozygosity , Medulloblastoma , Microsatellite Repeats , Neural Plate , Polymerase Chain ReactionABSTRACT
Phosphatase and tensin homology deleted on chromosome 10 (PTEN) is a tumor suppressor with dual protein and lipid phosphatase activity.PTEN is involved multisystem diseases and cancer,though the mechanisms of PTEN regulation are far from clear.Recent advances concerning regulation of PTEN including protein-protein interaction,phosphorylation,ubiquitination,oxidation and acetylation will be discussed.
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PURPOSE: This study was performed to determine the relationship between PTEN and vascular endothelial growth factor (VEGF) expression and to assess their roles in the tumor-induced angiogenesis and tumor progression in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissues, from 96 patients diagnosed with NSCLC, were evaluated for VEGF and PTEN expression using immunohistochemical methods. The results of the expression pattern of VEGF alone, or in combination with PTEN expression, were compared with clinicopathological parameters. RESULTS: VEGF expression was seen in 54 (56.3%) of the 96 NSCLCs evaluated, and was significantly correlated with histological type, and seen more frequently in adenocarcinomas compared to the other histological types (p<0.05). There were no significant associations between VEGF expression and tumor size, lymph node metastasis and stage. The microvessel density (MVD) determined by CD34 staining were significantly higher in tumors with VEGF expression (62.9+/-21.8) than those without (55.1+/-15.1). Loss of PTEN expression was seen in 33 (34.4%) of the 96 NSCLCs evaluated. VEGF expression was more frequently detected in the tumors with loss of PTEN expression (69.7%) than in those with PTEN expression (49.2%). When the combined VEGF/ PTEN phenotypes were divide into two groups; group I (VEGF-/PTEN+) and group II (VEGF-/ PTEN-, VEGF+/PTEN+, VEGF+/PTEN-), a significant correlation was also seen between the groups and the histologic types. There was a trend for the tumors in group II to show more frequent lymph node metastasis (50.0%) than those in group I (31.5%), although there was no statistical significance. The MVDs were significantly higher in group II (63.1+/-20.7) than in group I (53.4+/-17.2). CONCLUSION: These findings demonstrate an inverse correlation between the expressions of PTEN and VEGF. It is possible that PTEN may repress VEGF expression, and modulate VEGF-mediated angiogenesis, which suggests further analysis of the complex phenomenon of neo-angiogenesis in NSCLC is essential.
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Humans , Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Chromosomes, Human, Pair 10 , Lymph Nodes , Microvessels , Neoplasm Metastasis , Phenotype , Vascular Endothelial Growth Factor AABSTRACT
Phosphatase and tensin homology deleted on chromosome 10 (PTEN) plays an important role in the proliferation,migration,differentiation,apoptosis and synapse establishment of nervous system.Elucidation of PTEN function is helpful to understand the mechanisms of neural development,and thus may find new therapies for diseases in central nervous system using PTEN as a target.
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Purpose:To clarify roles of overexpression of phosphorylated Akt(p-Akt) and loss of phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in biological behavior of non-small-cell lung cancer(NSCLC). Methods:Immunohistochemical staining was used to determine the expression of p-Akt and PTEN in 20 cases of normal lung tissues and 102 patients with NSCLC.Results:Negative p-Akt expression and positive PTEN expression were found in normal lung tissues, while the positive incidences of p-Akt expresssion and loss of incidences of PTEN expresssion in NSCLC were 41.2% (42/102) and 46.1% (47/102)respectivtly.The overexpression of p-Akt and loss of PTEN expression were correlated to degree of differention of cancer, metastasis(including lymph node), and clinical stages. A significant negative correlation was observed between expression of p-Akt and PTEN(Phi r=-0.425,P