TY - EJOU
AU - PETROVIC, ISIDORA
AU - MILIVOJEVIC, MILENA
AU - ARSENIJEVIC, ANA
AU - LAZIC, ANDRIJANA
AU - GRUJICIC, NATASA KOVACEVIC
AU - SCHWIRTLICH, MARIJA
AU - POPOVIC, JELENA
AU - STEVANOVIC, MILENA
TI - Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells
T2 - BIOCELL
PY - 2021
VL - 45
IS - 5
SN - 1667-5746
AB - Genetic and molecular heterogeneity, together with intrinsic and acquired resistance to therapy, represent the
major obstacles to the successful treatment of different types of breast carcinoma. Increasing evidence demonstrates that
SOX transcription factors in breast carcinomas could act both as oncogenes and tumor suppressors and have been
associated with tumor stage and grade, poor prognosis, and therapy resistance. Both SOX2 and SOX18 overexpression has been correlated with poor prognosis in breast carcinomas, and these genes are recognized as potential
antitumor targets. Our aim was to evaluate the effect of retinoic acid (RA), a well-known cyto-differentiating agent,
on breast carcinoma cells in vitro and to investigate the potential of RA treatment to modify the expression of SOX2 and SOX18 genes. By applying various experimental approaches, we evaluated the effect of RA on basic cellular
processes in SK-BR-3 and MCF7 breast carcinoma cell lines. We have shown that RA inhibits cell growth, reduces the
number of Ki-67 positive cells, and causes cell-cycle arrest. RA effect was more prominent in SK-BR-3 cell line that
lacks SOX2 expression, including a higher decrease in cell viability, reduction in colony formation, and significant
remodeling of cellular structure. We have shown that RA treatment led to the downregulation of SOX2 expression in
MCF7 cells and to the reduction of SOX18 expression in both cell lines. By functional analysis, we showed that the
anti-proliferative effect of RA in both cell lines was not based on the activity of stemness marker SOX2, pointing to a
SOX2-independent mechanism of action. The ability of RA to reduce SOX2/SOX18 expression raises the possibility
that these genes can be used as biomarkers to distinguish RA-responders from non-responders. Together, our study
shows that the response of breast carcinoma cell lines to RA treatment may vary, highlighting that the development
of RA-based therapy should consider differences in breast carcinoma subtypes.
KW - Breast carcinoma
KW - Anti-proliferative activity
KW - Transcription factors
KW - MCF7 cell line
KW - SK-BR-3 cell line
DO - 10.32604/biocell.2021.015817