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Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis. This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest-a phenomenon known as mitotic catastrophe, which is followed by immediate cell death apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate.
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Niemann-Pick disease type C (NPC) is a fatal,neurovisceral lipid storage disease,neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons,progressive neuronal loss,neurofibrillary tangles (NFTs) formation,and axonal spheroids (AS).Cytoskeletal pathology including accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological hallmark of the mouse model of NPC (npc mice).With a goal of elucidating the mechanisms underlying the lesion formation,we investigated the temporal and spatial characteristics of cytoskeletal lesions and the roles of cdc2,cdk4,and cdk5 in lesion formation in young npc mice.Cytoskeletal lesions were detectable in npc mice at three weeks of age.Importantly,concomitant activation of cdc2/cyclin B 1 kinase and accumulation of a subsequently generated cohort of phospho-epitopes were detected.The activation of cdk4/cyclin D1 and cdk5/p25 kinases was observed during the fourth week of life in npc mice,and this activation contributed to the lesion formation.We concluded that the progression of cytoskeletal pathology in npc mice older than four weeks is accelerated by the cumulative effect of cdc2,cdk4,and cdk5 activation.Furthermore,cdc2/cyclin B1 may act as a key initial player one week earlier.Targeting cell cycle activation may be beneficial to slow down the NPC pathogenesis.
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Objective To explore the role and mechanism of keratin 19 (KRT19) in breast cancer.Methods Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine KRT19 levles in 35 cases of breast cancer tissues and normal tissues.The correlation between KRT19 levels and clinical property of breast cancer was analyzed.Meanwhile,the expression levels of KRT19 in several breast cancer cells and mammary epithelial cell Michigan cancer foundation (MCF)-10A were evaluated by qRT-PCR assay.Over-expressed and knocked-down KRT19 in breast cancer ceils,3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was performed to detect the proliferation and chemosensitivity of these cells.The ability of forming colon of these breast cancer cells with treated KRT19 was studied via colony-forming unit assays.Western blot assay was performed to determine expression levels of ceil cycler related proteins.Results KRT19 was upregulated in breast cancer tissues comparing to normal tissues.KRT19 was positively related to tumor node metastasis (TNM) stage and distant metastasis of breast cancer.Similarly,KRT19 was highly expressed in breast cancer cells compared to mammary epithelial cell MCF-10A.The proliferation and colony-forming ability was significantly enhanced in MCF-7 cell with o,verexpressed KRT19.MTS assay showed that chemosensitivity of MCF-7 cells with overexpression of KRT19 was much more remarkably reduced than the control group.However,knocking down KRT19 in breast cancer cells MDA-MB-231 got the opposite results.Western blot assay suggested that KRT19 could obviously upregulated cyclin-dependent kinase 1 (CDK1) but not p27 expression levels.Conclusions KRT19 was upregulated in breast cancer tissues and was positively related to TNM stage and distant metastasis of breast cancer.KRT19 can significantly enhance proliferation and chemoresistance of breast cancer cells via upregulating CDK1.
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Purpose To investigate the relationship between HPV infection and p53,p16,EGFR expression and prognosis in patients with salivary adenoid cystic carcinoma (ACC).Methods Totally 76 cases of adenoid cystic carcinoma specimens were selected,PCR-reverse dot blot hybridization was used to detect infection of HPV and SP immunohistochemical method was adopted to detect the expression of p53,p16,EGFR,Cdc2 in tumor tissues.Clinical data were collected and all the patients were followed up.The Kaplan-Meier method was used to estimate median overall survival and the Log-rank test to compare survival curves.Cox regression model was used for multivariate analyses.Results Infection rate of HPV in adenoid cystic carcinoma tissues was 0(0/76).The expression rate of p53,p16,EGFR,Cdc2 protein in adenoid cystic carcinoma tissues were 76.3％ (58/76),57.9％ (44/76),60.5％ (46/76) and 64.5％ (49/76)respectively.There was no correlation of the expression of p53,p16,EGFR and Cdc2 with gender,age,tumor location,TNM stage and histological type of patient.Kaplan-Meier survival analysis showed that EGFR-positive patients had shorter median overall survival rate (OS) than the negative ones (x2 =19.111,P ＜ 0.001).EGFR-positive patients had shorter median progression-free survival rate (PFS)than the negative ones (x2 =6.621,P ＜ O.01).Cdc2 positive patients had shorter median OS than the negative ones (x2 =3.870,P ＜ 0.05).Cdc2 positive patients had shorter median PFS than the negative ones (x2 =6.755,P ＜0.01).Cox regression analysis showed that expression of EGFR and Cdc2 was independent risk factors for the prognosis of patients with salivary gland ACC (relativerisk=13.417,13.075,P＜0.001).Conclusion There is no HPV infection detected in adenoid cystic carcinoma tissues.p53,p16,EGFR and Cdc2 are positively expressed in most salivary adenoid cystic carcinoma,p16 is unsuitable as a surrogate for HPV infection status of patient with ACC.Expression of EGFR and Cdc2 is independent risk factors in the prognosis of patients with salivary gland ACC.For the EGFR or Cdc2 positive patients should be followed up closely.
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Aim To explore the effects of ophiopogo-nin-B (OP-B)on cell cycle and mitosis in non-small cell lung cancer (NSCLC)H460 cells in vitro and the underlying mechanisms. Methods TUNEL immuno-histochemical assay was used to detect the change of the nuclear matter. DAPI staining was used to detect the change of the nuclear morphology and the mitosis status. Meanwhile,Western blot was performed to de-termine the protein level of the proteins regulating cell cycle and mitosis. Results OP-B significantly arres-ted cell cycle in G0 / G1 phase and inhibited the mitosis in H460 cells at the concentration of 10 μmol·L - 1 . Meanwhile,it inhibited the protein level of cyclinD1, cyclinB1,and up-regulated the expression of Myt and the phosphorylation level of Cdc2. Conclusion OP-B inhibits cell mitosis in A549 cells through Myt/ Cdc2 signaling pathway.
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Purpose To study the expression of p53, p21 and Cdk1/p34cdc2 in the laryngeal cancer and its margin tissues and to ex-plore their relationship with local recurrence of laryngeal cancer. Methods A total of 85 patients with early laryngeal cancer were se-lected randomly during 2004 to 2010 in Tangshan Union Hospital, Hebei, China. SP immunohistochemical method was used to detect the expression of p53, p21 and Cdk1/p34cdc2 in the tumor and margin tissues. Pathological data were collected for follow-up. Results In more than 2 years of follow-up study, 14 of 85 patients with laryngeal cancer presented with recurrence (recurrent group), while 71 patients without recurrence (none recurrent group). The positive rate of p53 protein in laryngeal cancer and its margin tissues was 60. 0% and 36. 5%, respectively, the positive rate of p21 protein in laryngeal cancer and its margin tissues was 38. 8% and 21. 2%, respectively. The positive rate of Cdk1/ p34cdc2 in laryngeal cancer and its margin tissues was 70. 6% and 29. 4%, respectively. p53 protein in the surgical margin of the recurrent group and non recurrent group was 71. 4% and 29. 6% (P = 0. 003), that of p21 was 50. 0% and 15. 5%, (P =0. 004) and Cdk1/ p34cdc2 was 57. 1% and 23. 9% (P =0. 013), respectively. There was no correlation between expression of p53 with p21 protein and Cdk1/ p34cdc2 protein(P > 0. 05). Conclusion p53, p21 and Cdk1/ p34cdc2 may be involved in the occurrence, development and recurrence of laryngeal squamous cell carcinoma. Overexpression of p53, p21 and Cdk1/ p34Cdc2 in the surgical margin is closely related to local recurrence of laryngeal cancer.
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Objective To investigate the effect of artesunate on the cell cycle of human multiple myeloma RPMI8226 cells and explore the related molecularmechanisms. Methods RPMI8226 cellswere treated with 0, 25, and 50 pg/mL artesunate. The morphology change of cells was observed under transmission electron microscope, the cell cycle distribution was detected by flow cytometry, and the expression of cyclin B1 and p34cdc2 protein was examined by Western blotting analysis. Results After treated with 50 pg/mL artesunate for 48 h, most RPMI8226 cells showed characteristic morphology of apoptosis. With the increase of artesuate concentration, the proportion of RPMI8226 cells in G0/G1 phase was significantly decreased (P<0. 05) and that of cells in G2/M phase was significantly increased (P<0.05), suggesting that artesunate induced noticeable G2/M arrest. Cyclin B1 level was increased and the p34cdc2 level was decreased with the increase of artesuate concentration. Conclusion Artesunate can induce G2/M arrests in RPMI8226 cells, which may be related to the increasedcyclin B1 expression and decreased p34cdc2 expression.
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Axonal regeneration is critical for functional recovery following neural injury. In addition to intrinsic differences between regenerative responses of axons in peripheral versus central nervous systems, environmental factors such as glial cells and related molecules in the extracellular matrix (ECM) play an important role in axonal regeneration. Schwann cells in the peripheral nervous system (PNS) are recognized as favorable factors that promote axonal regeneration, while astrocytes and oligodendrocytes in the central nervous system (CNS) are not. In this review, we evaluate the roles of Schwann cells and astrocytes in axonal regeneration and examine recent evidence that suggests a dual function of astrocytes in regenerative responses. We also discuss the role of Cdc2 pathways in axonal regeneration, which is commonly activated in Schwann cells and astrocytes. Greater insight on the roles of glial cells in axonal regeneration is key to establishing baseline interventions for improving functional recovery following neural injury.
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Astrocytes , Axons , Central Nervous System , Extracellular Matrix , Neuroglia , Oligodendroglia , Peripheral Nervous System , Regeneration , Schwann CellsABSTRACT
PURPOSE: The molecular mechanisms that are responsible for the initiation and progression of breast cancers are largely unknown. This study was to analyze the cyclin B1, cdc2, p53 and p16 tumor suppressor genes in human breast cancer. MATERIALS AND METHODS: To investigate the role of cyclin B1, cdc2, p53 and p16 in the pathogenesis and progression of breast carcinomas, 98 cases of breast cancers were examined by immunohistochemical method. The correlations of cyclin B1, cdc2, p53 and p16 expression with various clinico-pathologic findings were analysed. RESULTS: In the normal breast tissues, cyclin B1, cdc2 and p16 were weakly expressed, while p53 was not expressed. On the other hand, cyclin B1, cdc2, p53 and p16 were overexpressed in breast cancer, showing correlation between the expression of cyclin B1 and cdc2 and breast cancers (p=0.00). The overexpressions of cdc2 and p16 were correlated with an infiltrative tumor border pattern and this was statistically significant (p<0.05). In addition, the overexpression of cdc2 was correlated with histologic high grade carcinomas (p=0.00). CONCLUSION: Cyclin B1 and cdc2 appeared to be involved in the genesis or progression of breast cancers. In addition, the overexpressions of p16 and p53 may play important roles in more aggressive tumor and the overexpression of cdc2 is associated with progression of tumor to a higher grade of breast carcinomas. The deranged overexpressions of cyclin B1, cdc2, p16 and p53 may play an important role in human breast carcinogenesis.
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Adult , Aged , Female , Humans , Middle Aged , Breast Neoplasms/genetics , Cyclin B/genetics , Cyclin B1/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , Gene Expression Regulation, Neoplastic , Immunohistochemistry , Tumor Suppressor Protein p53/geneticsABSTRACT
Objective Proliferative cholangitis (PC) is responsible for stone recurrence and biliary restenosis, this study was to investigate the and-proliferative effect of CDC2 kinase shRNA on PC. Methods The common bile duct of PC rat model was given an intralumenal administration of 0. 5 ml of CDC2 kinase shRNA. Results CDC2 kinase shRNA treatment effectively inhibited the expression of CDC2 kinase,PCNA, and procollagen I , resulting in the inhibition of hyperplasia of biliary epithelium, submucosal gland, and collagen fibers. Also, the lithogenic potentiality of PC decreased due to the inhibition of endogenous β-glucuronidase secretion. Conclusion The anti-proliferative effect of CDC2 kinase shRNA on PC may prevent biliary restenosis and stone recurrence.
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Objective: To study the expression of p34cdc2 and cyclin B1 in human cervical carcinoma, and the relationship between their expression and clinicopathologyical features of cervical cancer. Methods: A quantitative real-time reverse transcription polymerase chain reaction and Western blotting assay were used to analyze the expression levels of p34cdc2 and cyclin B1 mRNA and protein, respectively, in fresh invasive cervical cancer (n = 62) and control cervical tissues (n = 15). Results: The expression levels of p34cdc2 and cyclin B1 mRNA and protein were significantly higher in cancer tissues than those in control cervical tissues (P = 0.004, P = 0.013; P = 0.016, P = 0.029), and mainly displayed overexpression. Significant positive correlation was found between the expression of p34cdc2 and cyclin B1 mRNA (r = 0.527, P = 0.001) and protein (r = 0.432, P = 0.022) in cervical cancer tissues. A statistical significance was found between the expressions of p34cdc2/cyclin B1 mRNA and lymphatic metastasis in cervical cancer (P = 0.038, P = 0.001). No statistically significant association was found between the age, histological types, the differentiation degree, clinical stages and expression of p34cdc2/cyclin B1 (P > 0.05). Conclusion: p34cdc2 and cyclin B1 are important molecules in regulation of cervical carcinogenesis. Over-expression of p34cdc2/cyclin B1 stimulates cervical cancer cells to overcome G2/ M checkpoint and enter M phase in cell cycle. The high-expression of p34cdc2/ cyclin B1 might become a novel biomarker for studying the mechanism underlying the tumorigenesis and lymphatic metastasis of cervical cancer.
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Objective To describe the spatial and temporal characteristics of neurofibrillary tangles (NFT) in brains of patients with Niemann-Pick disease type C (NPC). Methods In order to analyze formation of NFT in NPC, the brains collected from 17 patients with NPC aged from 7 months to 55 years old were investigated using antibodies against the protein tau and the specific proteins in mitotic phase. Results Typical NFT could be detected in the parahippocampns of a NPC patient as early as at 4 years old. The number of NFT were increasing along with the time. Gradually, the hippocampus and other regions of the temporal lobes and the frontal lobes would be affected with the time. Immunohistochemically, the NFT formed the shape similar to NFT seen in AD brains, without the presence of senile plagues. Interestingly,mitosis-phase markers appeared in the degenerating NPC neurons prior to hyperphesphorylation of tau and formation of NFT. Conclusions The formation of NFT does not result from aging, for there is no close relation between the presence of senile plagues and the formation of NFT. Ectopic activation of cdc2/cyclinB1 kinase complex might be an early event leading to NFT formation. Antagonist of the kinase complex may potentially slow down the formation of NFT.
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PURPOSE: Cell cycle progression is regulated by interactions of specific cyclins and cyclin dependent kinases (CDKs) at the G1-S and G2-M checkpoints and cell cycle deregulation plays a major role in carcinogenesis of human cancers. PATIENTS AND METHODS: To investigate the role of cell cycle regulators in the pathogenesis and progression of human gastric cancers, 23 cases of gastric carcinomas were examined for the expression of cyclin B1, p34cdc2, p27(Kip1) and p53 by immunohistochemical methods, and gene expression was correlated with various clinicopathologic findings. RESULTS: Out of 23 cases studied, cyclin B1 was diffusely expressed in 20 cases (87.0%), p34cdc2 in 14 cases (60.9%) and p53 in 12 cases (52.2%), whereas in normal gastric tissues, cyclin B1 and p34cdc2 were weakly expressed and p53 was not expressed. In contrast, p27(Kip1) was expressed in only 8.7% of gastric carcinomas compared with 78.3% of normal gastric tissues. There was correlation between the expression of cyclin B1 and expression of p34cdc2 (p=0.002), between the expression of cyclin B1 and loss of p27(Kip1) (p=0.025), and between the expression of p34cdc2 and loss of p27(Kip1) (p=0.065). In addition, expression of cyclin B1 was correlated with regional lymph node metastasis (p=0.032). CONCLUSION: Our results indicate that cyclin B1 and p34cdc2 are involved in the genesis or progression of gastric cancers. Furthermore, overexpression of cyclin B1 may play an important role in lymph node metastatic potential of gastric cancer. Thus, abnormal expression of cyclin B1 and CDKs, overexpression of p53 and loss of p27(Kip1) expression may play important roles in human gastric carcinogenesis.
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Adult , Aged , Female , Humans , Male , Middle Aged , CDC2 Protein Kinase/metabolism , Cyclin B/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Prognosis , Stomach Neoplasms/diagnosis , Tumor Suppressor Protein p53/metabolismABSTRACT
PURPOSE: Recent studies have suggested that p53 regulates the G2 checkpoint in the cell cycle and this function is required for the maintenance of genomic integrity. In this study, we addressed a role of p53 in escaping from cell cycle G2 arrest following DNA damage. MATERIALS AND METHODS: Cell cycle checkpoint arrest in the human colon cancer cell line HCT116 and its derivatives carry p53 or p21 deletions, were examined by FACS analysis, immunoprecipitation, Western blot and IP-kinase assay. RESULTS: While the cells with functional p53 were arrested at both the G1 and G2 checkpoints, the p53-deficient cells failed to arrest at G1, but they were arrested at G2. However, the p53-deficient cells failed to sustain G2 checkpoint arrest and they entered mitosis earlier than did the p53-positive cells and so this resulted in extensive cell death. Cdc2 kinase becomes reactivated in p53-deficient cells in association with entry into mitosis, but not in the p53-positive cells. Upon DNA damage, the p21-deficient cells, like the p53-negative cells, not only failed to repress cdk2- dependent NF-Y phosphorylation, but they also failed to repress the expression of such cell cycle G2-regulatory genes as cdc2, cyclin B, RNR-R2 and cdc25C, which have all been previously reported as targets of NF-Y transcription factor. CONCLUSION: p53 is essential to prevent immature escaping from cell cycle G2 checkpoint arrest through p21-mediated cdk2 inactivation, and this leads to inhibition of cdk2-dependent NF-Y phosphorylation and NF-Y dependent transcription of the cell cycle G2-rgulatory genes, including cdc2 and cyclin B.
Subject(s)
Humans , Blotting, Western , CCAAT-Binding Factor , CDC2 Protein Kinase , Cell Cycle Checkpoints , Cell Cycle , Cell Death , Cell Line , Colonic Neoplasms , Cyclin B , DNA Damage , G2 Phase , Immunoprecipitation , Mitosis , Phosphorylation , Phosphotransferases , Transcription Factors , Tumor Suppressor Protein p53 , United NationsABSTRACT
BACKGROUND: Cell cycle progression is governed by cell cycle regulators and inhibitors such as the cyclin dependent kinases (CDK), p27(Kip1), p21(WAF1/Cip1) and p53. The purpose of this study was to correlate expressions of p34(cdc2), p27(Kip1), p21(WAF1/Cip1) and p53 with the various clinicopathologic prognostic parameters of human breast cancers. METHODS: The paraffin-embedded tissue sections from 102 patients with human breast carcinomas were examined by performing immunohistochemical staining. The primary antibodies used for immunohistochemical staining were mouse monoclonal antibody to human p34(cdc2), p27(Kip1), p21(WAF1/Cip1), p53, ER and PR. RESULTS: The expression rates of p34(cdc2), p21(WAF1/Cip1) and p53 were 29.3%, 40.2% and 49.1% in breast carcinomas, respectively. In normal breast tissues, p34(cdc2), p21(WAF1/Cip1) and p53 were not expressed. The p34(cdc2) was expressed in the cytoplasm of cancer cells. The expression rate of p27(Kip1) was 29.3% in breast carcinomas and 100% in normal breast tissues, so the loss of p27(Kip1) expression in breast cancer was noted. The high expression of p21(WAF1/Cip1) in neoplastic cells was associated with the p53 expression (p=0.03). The expression of p27(Kip1) was correlated with that of the progesterone receptor (PR) (p=0.04) and the expression of p21(WAF1/Cip1) was correlated with that of positivity for estrogen receptor (ER) (p=0.04) and PR (p=0.04). No correlation was demonstrated between the mean patient survival and the expression rate of p34(cdc2), p27(Kip1), p21(WAF1/Cip1) and p53. CONCLUSIONS: The loss of the normal cell growth cycle by the abnormal expression of cyclin dependent kinases and their inhibitors and the steroid hormones may play an important role in human breast carcinogenesis. The p53 dependent p21(WAF1/Cip1) pathway, the p27(Kip1) protein loss and the cdc2 overexpression were important in development and progression of human breast cancer.
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Animals , Humans , Mice , Antibodies , Breast Neoplasms , Breast , Carcinogenesis , Cell Cycle , Cyclin-Dependent Kinases , Cytoplasm , Estrogens , Receptors, ProgesteroneABSTRACT
Objective To investigate the role of expressions of pituitary tumor transforming gene(PTTG) and p27 in glioma,and explore the relationship between the expressions of them and cell cycle regulation.Methods Specimens of 40 patient with gliomas were divided into gradeⅠ:8 cases,gradeⅡ:10 cases,gradeⅢ:13 cases, gradeⅣ:9 cases,PTTGmRNA and p27mRNA were detected by reverse transcription polymerase chain reaction (RT-PCR),and their expressions of PTTG,P27,CDK4 protein were detected by immunostaining assay using strep- tavidin-peroxidase(SP) method.Results The expressions of PTTGmRNA in gradeⅠ～Ⅳwere (0.907?0.065),(1.109?0.083),(1.312?0.089),(1.499?0.215) respectively,there was significant difference among the groups(P
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To investigate the role of cyclin B1 and cdc2 in the pathogenesis and progression of malignant lymphoma, 68 cases of nodal non-Hodgkin's lymphoma were examined about the expression of cyclin B1 and cdc2 along with p53 and Ki-67 by immunohistochemical method. The correlation of their expression with various clinicopathologic findings was also analyzed. Cyclin B1 and cdc2 were diffusely expressed in 39 cases (57.4%) and 54 cases (79.4%) out of 68 cases studied, respectively. The mean labeling indices of cyclin B1 and cdc2 in malignant lymphoma were 31.9% and 68.0%, respectively. In normal lymphoid tissues, cyclin B1 and cdc2 were expressed predominantly in the germinal center with mean labeling indices of 13.9% and 28.3%, respectively. The correlation between the expression of cyclin B1 and cdc2 was noted (p=0.013). The expression of Ki-67 was correlated with that of cyclin B1 (p=0.023) and marginally correlated with that of cdc2 (p=0.056). The expression of cdc2 and p53 in complete remission group to chemotherapy was lower than that of progressive disease group (p=0.047, p=0.049). In multivariate analysis, the clinical stage alone showed significance on overall survival (p=0.049). In conclusion, cyclin B1 and cdc2 appeared to be involved in the genesis or progression of malignant lymphoma and cdc2 can be a useful marker for response to chemotherapy.
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Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , CDC2 Protein Kinase/biosynthesis , Cyclin B/biosynthesis , Cyclin B1 , Immunohistochemistry , Ki-67 Antigen/biosynthesis , Lymph Nodes/metabolism , Lymphoma, Non-Hodgkin/metabolism , Palatine Tonsil/metabolism , Predictive Value of Tests , Prognosis , Survival Analysis , Tumor Suppressor Protein p53/biosynthesisABSTRACT
Objective:To investigate the expression of c myc and cdc2 gene in iliac femoral arteries of rabbits fed with high cholesterol diet. Methods:Totally 24 New Zealand rabbits fed with high cholesterol and high lipid diet were chosen for the experiment. In treated groups,the iliac femoral arteries were dilated by balloon catheter in 2 week high lipid diet fed rabbits. After 6 8 weeks,angiography was performed to detect the stenosis in iliac femoral,and ballon dilation was carried out when stenosis beyond 50%. Expression of c myc and cdc2 mRNA (24 h following balloon dilation) and their proteins (2 weeks following balloon dilation) were measured by means of RT PCR and immunohistochemistry (GISS) methods. Results: Expressions of c myc,cdc2 mRNA and their proteins in dilated arteries were all increased 24 h and 2 weeks following balloon dilation. Immuno positive particles were mainly located at nuclei of SMC in neotima layer,and a little at cytoplasma. Conclusion: Expressions of c myc,cdc2 mRNA and their proteins are increased in arteries following angioplasty. It is indicated that c myc and cdc2 may play an important role in neointimal formation after angioplasty.