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Abstract
IntroductionBreast 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.MethodsFollowing 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.ResultsRBBP6 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.ConclusionThe effect of RBBP6 on cell proliferation and apoptosis induction in breast cancer seems to be cell line-dependent based on p53 status.
Highlights
Breast cancer is the most common malignancy amongst women and has a higher incidence rate than lung cancer
The results suggest the role of RBBP6 in p53 expression and activation. p53 is the genomic guardian of the cell apoptosis in the guardian machinery of cell survival or death and plays a crucial role in deciding whether cells progress through cell cycle even if damaged
It is evident that the genotypic status of p53 in MCF-7 and MDA-MB-231 breast cancer cell lines plays a critical role in the way they respond to RBBP6-targeting treatment and/or co-treatment with apoptosis-inducing therapeutic agents
Summary
Breast cancer is the most common malignancy amongst women and has a higher incidence rate than lung cancer. Breast cancer remains a female-related health problem on a global scale, accounting for over a million newly estimated cases and the counts are still on the rise.[1] Uncontrolled cell growth and metastasis are considered the hallmarks of breast tumorigenesis and of most other cancers
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