Expression And Pathological Significance Of PTEN, P53 And BAG-1 In Triple-negative Breast Carcinoma

ObjectiveTo investigate the expressions of PTEN, p53 and BAG-1 protein in a series of triple-negative breast cancers and to relate these expression to clinicopathologic features, and then to discuss the association between PTEN loss, p53 mutations and BAG-1 expression.Methods1.The PTEN small inteifering RNA(PTEN-si RNA) was transfected into human Triple-negative breast cancer cell-line MDA-MB-231 by liposometransfection method to knock down the expression of PTEN. The cells were divided into 3 groups:experimental group with PTEN-si RNA, control group with si RNA that did not impact any gene, blank control group without any transfection.Real-time PCR and Western blotting were conducted to detect the expression of PTEN after transfection.2.Changes of invasion and migration in the cells were performed using transwell invasion and migration assay. Western blotting was used to detect the expression of PTEN,p53 and BAG-1 proteins respectively.3.A total of 89 formalin-fixed and paraffin-processed triple-negative breast cancer cases who from The First Affiliated Hospital of Liao ning Medical University were tested for PTEN, p53 and BAG-1 by immunohistochemistry. The resulting slides were scored for proportion and intensity of staining.Results1. As compared with control groups, the expression of PTEN m RNA and protein in the experimental group was significantly reduced(P<0.01),suggesting PTEN gene was silenced in MDA-MB-231 cell line successful Iy.2. The number of invasion(221±10.8)and migration(342±9.6)cells was significantly increased in experimental group than that in control groups(F=23.42,P<0.05;F=28.73,P<0.05).The p53 and BAG-1 proteins expression w ere upregurated after PTEN knock down(P<0.05).3. Loss of tumor nuclear and cytoplasmic staining for PTEN occurred in 44.9% of cases; The levels of p53,BAG-1 expression were seen in 47.2%,73% of cases, The expression of PTEN,p53 and BAG-1 were significantly associated with histological grade, lymphnode metastasis.Conclusions1. Compared with the other two control groups, the m RNA of PTEN-Si RNA group PTEN protein expression levels have reduced(P<0.05), indicating success PTEN gene silencing.2. The loss of PTEN could promote invasion and migration of MDA-MB-231 cells, and upregurate the p53 and BAG-1 proteins expression.3. Our clinical study supports PTEN, p53 expression and BAG-1 gene is closely related to the development of TNBC, there may be a synergistic effect. The combined detection of these three markers could indicate early pathological diagnosis and prognosis of breast carcinoma. But Further experiments to explore the prognostic and therapeutic role of PTEN,p53 and BAG-1 in TNBC are warranted...