Subcellular distribution of beta-catenin in cisplatin-treated triple negative breast cancer cells

CÓRDOBA ME; PENNACCHIO GE; AVILA MANIERO M; VARGAS ROIG LM; NADIN SB; FANELLI MA

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedades de Biociencias

Triple negative breast cancer subtype (TNBC) accounts for about15-20% of all invasive breast tumors. TNBC lacks expression of estrogen receptor (ER), progesterone receptor (PR) and Epidermal Growth Factor type 2 Receptor (HER2). To date not a single therapy has been applied, conventional cytotoxic chemotherapy is currently the only treatment option for TNBC. Unfortunately, some patients respond but others become resistant or eventually relapse. New therapeutic approaches are focused in the search of other molecular target and anticancer drugs not classically used for breast cancer treatment, such as platinum analogues (cisplatin). Aberrant expression of beta-catenin has been linked to tumor progression and has become a promising target for cancer therapy. The aim of this work was to study the functionality of beta-catenin exposed to cisplatin in human cell lines, MDA-MB231 (TN) and MCF10A (non-tumorigenic epithelial cell line). Cisplatin toxicity was evaluated by MTT. The localization of total and active beta-catenin was analyzed by confocal microscopy and the expression levels by WB. The IC50doses for MDA-MB231 and MCF10A were 91,48µM and 55,80µM,respectively. Cisplatin treatment induced localization of total and a ctive beta-catenin from the plasmatic membrane/cytoplasm to the nucleus in MDA-MB231, but no changes were observed in MCF10Acells. Expression levels of total and active beta-catenin decreased significantly (p≤0,05) with cisplatin exposure in MDA-MB231 cells whereas the levels of these proteins were not significantly modified in MCF10A cells. Our preliminary data show altered subcellular localization and expression levels of beta-catenin by cisplatin in TNBC cells.