Cancer Management and Research (Sep 2018)
RBBP6 expressional effects on cell proliferation and apoptosis in breast cancer cell lines with distinct p53 statuses
Abstract
Lesetja Raymond Motadi,1 Mashianoke Marcia Lekganyane,1 Pontsho Moela2 1Department of Biochemistry, Faculty of Agriculture, Science and Technology, North-West University (Mafikeng Campus), Potchefstroom, South Africa; 2Department of Genetics, Faculty of Science, University of Pretoria, Pretoria, South Africa Introduction: Breast cancer is the most common malignancy amongst women and has a higher incidence rate than lung cancer. Its tumor progression partially results from inactivation of p53 which is caused by overexpression of ubiquitous regulatory proteins possessing p53-binding domain. RBBP6 is regarded as one of the ubiquitous proteins because of its RING finger-like domain which enables it to possess E3 ligase activity. Thus, it has become a potential target in cancer treatment as it is highly expressed in various malignancies including cancer. However, it is not clearly defined 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. This study aims at evaluating the effects of RBBP6 on cell growth and apoptosis in breast cancer cell lines with different p53 expressions.Methods: Following the analysis at mRNA and protein levels in breast cancer tissue, RBBP6 expression was successfully manipulated using gene silencing and protein overexpression techniques in MCF-7 and MDA-MB-231 cell lines. The cells were co-treated with siRBBP6 and anticancer agents following apoptosis detection, which was confirmed by caspase 3/7 activity and quantification of apoptotic genes. Results: RBBP6 was overexpressed in breast cancer tissues that were classified as stages 3 and 4, while in stage 1, its expression was much lower. The MCF-7 cell line which expresses wild-type p53 was more sensitive to apoptosis induction than MDA-MB-231 which is a mutant p53-expressing cell line. These data suggest that RBBP6 silencing triggers significant levels of intrinsic apoptosis, and its overexpression appears to promote cell proliferation in wild-type p53-expressing MCF-7 cell line as opposed to MDA-MB-231 cells. Conclusion: The effect of RBBP6 on cell proliferation and apoptosis induction in breast cancer seems to be cell line-dependent based on p53 status. Keywords: breast cancer, p53, apoptosis, RBBP6
