Expression Of BRMS1 And MTA1 In Ovarian Cancer And Experimental Study Of Altered Their Expression

Objective:It had been reported that breast cancer metastasis suppressor 1 (BRMS1) was absent or mutation in many malignant tumors with high metastatic potential. BRMS1 mechanism of metastasis suppression was as an epigenetic regulator of metastasis-associated gene expression. Its expression was very low in ovarian cancer, and it inhibitted the invasion and metastasis of ovarian cancer cells. But the mechanism was knowed very little about BRMS1 regulation invasion and metastasis in this cancer. As a metastasis-associated gen, MTA1 participated in the progression of ovarian cancer. There was absent the report about the relation of BRMS1 and MTA1 in this cancer. So, this study investigated the expression of BRMS1 and MTA1 in ovarian cancer and whether they had correlation.Methods:Pathological examination of all specimens was stained with HE stain. Immanohistochemistrical SP method was used to detect the expression of MTA1 and BRMS1 in 46 cases of ovarian adenocarcinoma and 16 cases of normal ovarian tissue.Results:All the tissue pathological results were conincidence with the clinical pathological reports. BRMS1 and MTA1 were located in cell nucleus in normal ovarian tissue, but in cell nucleus and (or) endochylema in ovarian cancer tissue. The expression of BRMS1 in ovarian adenocarcinoma (21.74%) was significantly lower than those in normal ovarian tissues (93.75%), P<0.05. The expression of MTA1 in ovarian adenocarcinoma (82.61%)was significantly higher than those of normal ovarian tissues (37.50%), P<0.05. The inverse correlation between the expression of BRMS1 and MTA1 was observed (r =-0.314, p=0.03). The expression of BRMS1 and MTAl was correlated with surgical stage and clinical metastasis (P<0.05), but had no correlation with the patients histopathological grading (P>0.05).Conclusions:BRMS1 and MTA1 played an important role in the development of ovarian cancer. It was speculated that they could be antagonism in the progression in this cancer. Objective:The inverse correlation between the protein expression of BRMS1 and MTA1 was observed in the ovarian cancer tissue in the first part. It was speculated that they could be against in the development of this cancer. But how about were they in the ovarian cancer cell lines? So this study investigated the change of the cell migration, invasion and MTA1 expression in adaptive ovarian cancer cell lines when the BRMS1 protein was over-expression in it.Methods:PcDNA3.1(+)-BRMS1 plasmid was reconstructed, and the BRMS1 expression level was detected by Western blot in many ovarian cancer cell lines, and the adptive cell line was selected. The reconstruction plasmid was transfected in selected cell line, and the migration, invasion were tested by wound-healing assay, Transwell assay respectively. The expression levels of MTA1 were evaluated by Western blot. Then, the pcDNA3.1(+)-BRMS1 and pEGFP-Cl-MTAl plasmid cotransfection was done, the cell migration and invasion function was evaluated, the protein expression of BRMS1 and MTA1 was tested in the suitable cell line in compatible time.Results:The pcDNA3.1(+)-BRMS1 plasmid was successfully reconstructed. The BRMS1 protein expression was the lowest in SKOV3 than in the other ovarian cell lines. BRMS1 inhibitted the migration and invasion of SKOV3, and decreased the expression of MTA1 (P <0.05). After pcDNA3.1(+)-BRMS1 andβEGFP-C1-MTA1 plasmid cotransfection being done, the MTA1 expression and the function of migration and invasion of SKOV3 was partly recovered(P<0.05).Conclusions:BRMS1 inhibitted the migration and invasion of ovarian cell line through downregulation of the MTA1 protein expression. Objective:It has been reported that metastasis-associated gene 1(Mta1) is overexpressed in many malignant tumors with high metastatic potential. In addition, some studies indicated that MTA1 participated in invasion, metastasis, and survival of cancer cells by regulating cell migration, adhesion and proliferation. But the role of MTA1 is unclear in vitro in the development of cervical cancer cells. This study investigated whether and how MTA1 mediated cell proliferation, migration, invasion and adhesion in cervical cancer..Methods:MTA1 expression level was detected by Western blot in two cervical cancer cell lines of different invasion potentials. The effects of decreasing MTA1 expression level on SiHa cell apoptosis, cycle, proliferation, migration, invasion and adhesion were tested by flow cytometry, MTT, wound-healing assay, Transwell assay and adhesion assay, respectively. The expression levels of p53, E-cadherin, andβ-catenin activity were evaluated in untreated and treated cells with MTA1 siRNA. Results:1. MTA1 protein expression was significantly higher in SiHa than in HeLa. The potential of migration and invasion were significantly higher in SiHa cells. MTA1 protein expression was positive correlation well with the potential of migration and invasion in both cell lines.2. The cell invasion, migration and adhesion capabilities were decreased after inhibition of MTA1 expression mediated by Mta1-siRNA transfection in SiHa(P<0.05). However, no significant differences were found in cell apoptosis, cycle, and proliferation(P >0.05). In addition, E-cadherin and p53 protein levels were significantly up-regulated, whileβ-catenin was significantly down-regulated in SiHa transfected with the siRNA(P< 0.05).Conclusions:MTA1 played an important role in the migration and invasion of cervical cancer cells. It was speculated that the decreased migration and invasion capability by inhibiting the MTA1 expression in the SiHa cell line may be mediated through the altered expression of p53, and E-cadherin/β-catenin complex. MTA1 could serve as a potential therapeutic target in cervical cancer.