ABSTRACT
Objective To study the expression and significance of tumor metastasis suppressor gene-1(TMSG1) in esophageal squamous cell carcinoma (ESCC) and EC109 cells.Methods Immunohistochemistry S-P method was used to examine the expression of TMSG-1 protein in 136 cases of ESCC and 37 cases of normal esophageal mucosa.We analyzed the relationship between TMSG-1 and clinicopathological data of ESCC patients.EC109 cells were treated with 3 μg/mL of cisplatin (CDDP) in vitro for 24 h (the intervention group) and the control group was set up at the same time.The proliferation-inhibitory capability was analyzed with MTT assay.RT-PCR was used to examine the expression of TMSG-1 in the intervention group and the control group.Results The positive rate of TMSG-1 in ESCC and normal esophageal mucosa was 52.2％ (71/136) and 94.6％ (35/37),respectively.The expression of TMSG-1 in ESCC was significantly lower than that in normal esophageal mucosa (P＜0.05).The expression of TMSG-1 was related to TNM stage,differentiation degree and lymph node metastasis (P＜0.05).After EC 109 cells were treated with CDDP for 24 h,the proliferation inhibition rate was increased significantly compared with the control group (P＜0.01).RT-PCR results showed that the expression of TMSG-1 in the cells of the intervention group was significantly higher than that in the control group (P＜ 0.01).Conclusion The abnormal expression of TMSG-1 may play a role in the development and metastasis of ESCC.Examination of TMSG-1 may be useful for making diagnosis and guiding clinical therapy of ESCC.
ABSTRACT
Purpose To clarify the role of KAI1/CD82 in metastasis of nasopharyngeal carcinom and to evaluate the clinical efficacy of KAI1/CD82-expressing EPCs in the prevention of nasopharyngeal carcinoma.Method Umbilical vein-derived EPCs were infected with KAI1/CD82-expressing lenti-virus to get a KAI1/CD82-overexpressing EPC cell line (KAI1/CD82-EPCs).A xenograft mouse model of human nasopharyngeal carcinoma was established,and KAI1/CD82-EPCs were injected through the tail vein.The effect of the KAI1/CD82-EPCs on growth and metastasis of the xenograft was observed.Results Time required for tumor formation was 14.70 ± 3.81,15.05 ±3.85,14.20 ± 3.55 days respectively for the EPCs,EPCs-NC,and KAI1/CD82-EPCs groups,with no significant difference among the three groups (P =0.771).Weight of the xenograft was (1.388 ±0.204) g,(1.487 ±0.223) g,(1.485 ±0.234) g respectively for the EPCs,EPCs-NC,and KAI1/CD82-EPCs groups,with no significant difference (P =0.274).Rate of lung metastasis was 55％,45％ and 10％ for the EPCs,EPCs-NC,and KAI1/CD82-EPC groups,and the difference was significant (P =0.005).Number of metastatic lesions was 34.27 ± 5.35,38.44 ± 9.63,17.50 ± 3.54 for the three groups,and the difference was also significant (P =0.007).Immunohistochemistry indicated positive KAI1/CD82 expression in metastatic lesion of the KAI1/CD82-EPCs group,but no KAI1/CD82 expression in the EPCs group or EPCs-NC group.Conclusion KAI1/CD82-expressing EPCs inhibits lung metastasis of the xenograft mouse model of human nasopharyngeal carcinoma.
ABSTRACT
Breast cancer metastasis suppressor gene 1 (BRMS1) significantly reduces the invasion and metastasis of cancer cells.BRMS1 gene expression is decreased or deleted in the cells of various malignant tumors.BRMS1 gene can inhibit tumor cells invasion and metastasis by means of regulating gene transcription and protein translation by phosphoinositide signaling and nuclear factor-κB (NF-κB) signaling pathways,repairing intercellular communication and interacting with the mSin3-histone deacetylase (HDAC) complex,estrogen receptor and other proteins.BRMS1 gene may be a new target for the gene treatment of tumor metastasis.
ABSTRACT
OBJECTIVE To study the molecular mechanism of cisplatin(DDP)by which HeLa cell growth and proliferation are inhibited. METHODS Cultured HeLa cells were treated with DDP 0.02-75 μmol · L-1 for 24 or 48 h. CCK-8 assay was used to determine the cell proliferation. The wound scratch assay was used to detect the cell migration and invasion. Flow cytometry was used to detect the cell cycle arresting. q-PCR was used to test the expression of metastasis suppressor gene 1 (MTSS1)mRNA. Western blot was used to determine protein levels of MTSS1,phosphorylated-extra?cellular signal-regulated kinase(p-ERK) and phosphorylated-serine-threonine kinase(p-AKT). RESULTS Following the treatment with DDP for 24 or 48 h,the proliferation of HeLa cells was inhibited significantly (P<0.05),the value of the half inhibitory concentration (IC50) of cells was 4.14 and 11.82 μmol · L-1. Migration and invasion activity of HeLa cells were reduced according to the wound scratch assay(P<0.05). Flow cytometry results showed that the cell cycle was arrested at S phase. q-PCR results showed that MTSS1 mRNA expression changed with DDP in a concentration-dependent manner (r24 h=-0.965,P<0.01;r48 h=-0.953,P<0.01). Western blot showed that the protein levels of MTSS1,p-ERK and p-AKT expression declined significantly with the increase in DDP concentrations(p-ERK:r24 h=-0.875,P<0.01;r48 h=-0.966,P<0.01. p-AKT:r24 h=-0.831,P<0.01;r48 h=-0.863,P<0.01. MTSS1:r24 h=-0.969,P<0.01;r48 h=-0.988,P<0.01). CONCLUSION DDP treatment inhibits HeLa growth and proliferation by interfering with the MTSS1 expression and disturbing the activation of ERK and AKT signaling pathways.
ABSTRACT
Objective:To measure the expression of signal-induced proliferation-associated gene 1 (Sipa1) in gastric cancer and to determine its association with the clinicopathological characteristics and prognosis of patients with gastric carcinoma. Methods:The Sipa1 mRNA and Sipa1 protein expression levels in 43 fresh gastric carcinoma tissues and adjacent normal tissues were measured by real-time PCR and Western blot analysis. The Sipa1 protein expression levels in 122 paraffin blocks of gastric cancer and 64 normal gastric tissues were determined by substance P immunohistochemical technique. Results:The Sipa1 mRNA and Sipa1 protein levels in fresh gastric carcinoma tissues were significantly lower than those in adjacent normal tissues. Sipa1 protein was positive in 36.1%of the paraffin blocks of gastric cancer and in 73.4%of normal gastric tissues. The difference was statistically significant (P0.05). The five-year survival rates of Sipa1-negative patients were significantly lower than those of Si pa1-positive patients (P<0.01). Conclusion:Sipa1 expression is highly correlated with the biological behavior of gastric carcinoma and thus facilitates the evaluation of gastric carcinoma prognosis.
ABSTRACT
Objective: To study the effect of breast cancer metastasis suppressor gene 1 (BRMS1) on the migration of human breast cancer cells. Methods: An eukaryotic expression vector containing BRMS1 was constructed and was transfected into human breast cancer MDA-MB-231-HM cells by using Lipofectin 2000. Expression of BRMS1 mRNA was detected by real-time PCR. The migration of the cells was assayed by Transwell test. Meanwhile, three pairs of siRNA targeting BRMS1 were designed. The most effective siRNA was screened by real-time PCR and transfected into MDA-MB-231 cells. The migration ability of the transfected cells was detected. Results: Compared with the cells transfected with empty vector, the number of MDA-MB-231-HM cells on the underlayer of transwell decreased by 51.9% after stably transfected with BRMS1. One pair of siRNA was selected which could notably down-regulated BRMS1 expression at mRNA level. After siRNA transfection, the number of MDA-MB-231 cells on the underlayer of transwell increased by 17.9%. Conclusion: BRMS1 suppresses the migration of breast cancer cells, which indicates that BRMS1 may suppress cancer distant metastasis by inhibiting migration of breast cancer cells.
ABSTRACT
Objective:To investigate the influence of metastasis suppressor gene KAI1 on the proliferation,invasion and metastasis of endometrial carcinoma cell line AN3CA and HEC-1-B.Methods:The KAI1 cDNA was transfected into human endometrial carcinoma cells AN3CA and HEC-1-B via Lipofectamine 2000.The expression of KAI1 protein was ex- amined by Western blotting and flow cytometry before and after transfection.The proliferation ability of AN3CA and HEC- 1-B cells was observed by MTT assay and anchorage-independent growth assay.The changes of cell invasive ability were studied by transwell assays.Results:Stable expression of KAI1 protein was observed in AN3CA and HEC-1-B cells and on their surface after transfection with pcDNA3-KAI1 plasmid.Cells transfected with blank plasmid formed more colonies and had a larger size,with the colony forming rates being(54.2?3.1)% for AN3CA cells and(52.7?4.3)% for HEC- 1- B cells;the doubling time of AN3CA and HEC-1-B cells were 21.3 h and 20.1 h,respectively.Cells transfected with pcDNA3-KAI1 formed less colonies and had a smaller size,with the colony forming rates being(37.4?5.1)% for AN3CA cells and(32.1?3.7)% for HEC-1-B cells;the doubling time of AN3CA and HEC-1-B cells were 43.7h and 45.2 h,respectively.The cell proliferation abilities and colony-forming ability were significantly different between the two groups(P
ABSTRACT
PURPOSE: KAI1/CD82 gene is a recently identified metastasis suppressor gene on human chromosome 11p11.2. Alteration to or reduction of this molecule may allow tumor cells to invade the surrounding tissue and blood vessels. Decreased KAI1 expression seems to be involved in the progression of human prostate, lung and possibly breast cancer, and recently has been demonstrated in several colorectal cell lines. The aim of this study is to determine whether the gene is altered to investigate it in the progression and metastatic process of rectal carcinoma. In addition, its prognostic significance is also evaluated. METHODS: Total 108 tumor samples from primary, metastatic rectal carcinoma were prepared for immunohistochemical study with an anti-KAI1 polyclonal antibody. To analysis the correlation between KAI1 expression and clinicopathological parameter and to evaluate for relation expression and survival. RESULTS: Decrease of KAI1 protein expression was associated with the depth of invasion of tumor (P < 0.0001) and node metastasis (P < 0.05). Liver metastasis showed reduced KAI1 expression when compared with their corresponding primary tumor. Although there was a trend for deteriorating survival from patients with KAI1-positive tumors to those with KAI1-decreased and -negative tumors, it was not significant statistically (P Subject(s)
Humans
, Kangai-1 Protein
, Blood Vessels
, Breast Neoplasms
, Cell Line
, Chromosomes, Human
, Down-Regulation
, Genes, Tumor Suppressor
, Liver
, Lung
, Neoplasm Metastasis
, Prostate
, Rectal Neoplasms
ABSTRACT
Objective To study the effect of suppressing metastasis between KAI1 and ME491 on pancreatic cancer.Methods Normal pancreases and pancreatic cancers were analyzed using Northern blot,in situ hybridization and immunohistochemistry.Results The expression of KAI1and ME491 was higher in pancreatic cancer than that in normal pancreases,KAI1 expression was higher in pancreatic cancer without metastasis than that in pancreatic cancer with metastasis(P0.05).Conclusion The gene of KAI1 may be involved in the metastasis of pancreatic cancer,ME491 gene may have no effect on the metastasis of pancreatic cancer.
ABSTRACT
Purpose: To investigate the expression of KAI1 protein and its clinicopathological significance in breast cancer. Methods: Immunohistochemical staining ( S-P method) was used to detect the expression of KAI1 protein in specimens from 107 breast cancer and 30 adjacent normal breast tissues. Results: KAI1 protein positive rate in breast cancer tissues is significantly lower than that of adjacent nomal breast( P 0. 05). Conclusions: These data suggest that in advanced breast cancer, KAI1 is down-regulated and decrease in KAI1 ecpression plays an important role in the malignant progression of breast cancer. Therefore, detection of KAI1 protein might be a potentially valuable indicator for staging human breast cancer and predicting prognosis.
ABSTRACT
Purpose:To explore the expression of metastasis suppressor gene Kai1 in ovarian epithelial tumor and its significance.Methods:The expression of Kai1 protein in 108 samples of epithelial ovarian tumors and 12 of normal ovarian tissues was examined by S-P immunohistochemical staining.Results:The positive rates of Kai1 protein expression among malignant,borderline,benign and normal tumors were 26.6%,71.4%,73.3% and 83.3% respectively. The Kai1 protein expression in malignant tumors was obviously less than that in benign ones ( P 0.05). However,there was significant difference in Kai1 protein expression between samples of ovarian epithelial cancers with and without lymphonode metastasis ( P