The Role And Mechanism Of ABAT In Breast Cancer

Objectives The purpose of this study was to investigate the prognostic value of ABAT expression in breast cancer patients,and research the association between ABAT expression and ER expression status with patients prognosis.And we tested the hypothesis that ABAT overexpression can reduce the growth of breast cancer cells.Methods We used immunohistochemistry(IHC)to analyse the expression of ABAT and ER in breast cancer clinical species.The expression of ABAT and ER in breast cancer cells were analysed by Western-blotting.The prognostic value of the ABAT expression in ER-positive patients was estimated using the Kaplan-Meier method and compared to the log-rank test.The ABAT si RNAs were chemically synthesized by Ribobio(Guangzhou China).ABAT overexpression plasmid were constructed by ourself.We succeed constructed the breast cancer cell lines overexpression ABAT by lentivirus infection.MTT assays,Transwell chamber invasion assays were performed.ER negative MDA-MB-231 breast cancer cells which infected with ABAT overexpression lentivirus were injected into nude mice to examine the anti-tumor effects of ABAT.Results1.The online GOBO database showed that patients have a higher level of ABAT expression have a well survival prognosis.IHC showed that ABAT tended to be higher in ER positive patients.ABAT expression was significantly associated with ER status(P<0.050).The survival analysis revealed that ABAT low expression patients showed worse prognosis for DFS(P=0.001)and OS(P=0.002)compared to ABAT high expression patients.2.There was a positive correlation between the ABAT expression and ER expression in breast cancer cell lines.The protein expression level of ABAT was higher in ER positive MCF 7 cell lines than in the MDA-MB-231,MDA-MB-468,SK-BR-3 cell lines(ER negative).3.The MTT assay results showed that downregulation of the ABAT expression could promote the growth ability of MCF 7 cells and the ABAT overexpression MDA-MB-231 breast cancer cells showed a lower rate of growth compared with control group.Transwell chamber invasion assays showed that ABAT overexpression MDA-MB-231 cells had less invasiveness.4.Mices injected with ABAT overexpression MDA-MB-231 cells exhibited significantly lower rates tumor growth compared to control cells.IHC data showed that the upregulation of the ABAT expression can downregulate the expression levels of Ki-67 and EGFR in vivo.5.In ER positive breast cancer cell lines,downregulation the expression of ABAT may lead to the endocrine resistance.Conclusions Our study showed that there was a positively correlation between the ABAT expression and ER expression.ABAT tended to have a higher expression in ER positive breast cancer tissues.Patients with higher ABAT expression level may have well survival outcomes than patients with lower expression of ABAT protein in ER positive group.Our study demonstrates that overexpression ABAT protein can reduce the growth of breast cancer and downregulation the ABAT protein can promote the growth of breast cancer.In ER positive breast cancer cell lines,downregulation the expression of ABAT may lead to the endocrine resistance.The results of our present study suggest that ABAT expression could used as a new prognostic biomarker for ER positive breast cancer patients.