Abstract:
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 linedependent,
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.
