Abstract 3040: The expressional effects of RBBP6 in breast cancer cells are p53-dependent

Abstract

Abstract The incidence rate of breast cancer has increased beyond that of lung cancer, making it the most common malignancy among women. Breast tumor progression is partly because of p53 inactivation by overexpressed that possess p53 binding domain. RBBP6 forms a member of ubiquitous regulatory proteins because its RING finger-like domain has an E3 ligase activity. The overexpression of RBBP6 in several malignancies makes it a potential target in cancer management. However, there is no evidence on whether the effect of RBBP6 on cell growth and apoptosis is cell line dependent, more especially in breast cancer cell lines that have distinct p53 expression profiles. Therefore, the aim of this study was to evaluate the RBBP6 effects on cell growth and apoptosis in breast cancer cell lines with different p53 expression profiles. RBBP6 expression was successfully manipulated using gene silencing and protein overexpression techniques in MCF-7 and MDA-MB-231 cell lines. Transfected cells were co-treated with anti-cancer agents followed by apoptosis detection using confocal microscopy and flow cytometry, which was further confirmed by caspase 3/7 activity and quantification of apoptotic genes. RBBP6 was overexpressed in breast cancer tissues that were classified as stage 3 and 4 while in stage 1 it was expressed but at much lower levels. The wt. p53-expressing MCF-7 cell line was more susceptible to apoptosis induction as opposed to the mt. p53-expressing MDA-MB-231. RBBP6 silencing led to a significant accumulation of p53 expression in MCF-7 as compared to MDA-MB-231. Co-treatment with GABA and camptothecin seemed to sensitize the cells to apoptosis induction. These data suggest that RBBP6 silencing triggers significant levels of intrinsic apoptosis and over-expression appears to promote cell proliferation in wild-type p53-expressing MCF-7 rather than in MDA-MB-231 cells. In conclusion, the effect of RBBP6 on cell proliferation and apoptosis induction in breast cancer seem to be cell line dependent based on p53 status. Note: This abstract was not presented at the meeting. Citation Format: Pontsho Moela, Lesetja Motadi, Marcia Lekganyane. The expressional effects of RBBP6 in breast cancer cells are p53-dependent [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3040.