Epidermal growth factor receptor (EGFR) activation induces the expression of multidrug resistance associated protein 4 (MRP4/ABCC4) in a pancreatic cancer human cell line

SAHORES, A; DAVIO, C; LAGOS, R; IMPERIALES, J; GHANEM, CI; BAROSSO, I; MANAUTOU, JE

Rosario

Congreso; Reunión Anual de la Sociedad Argentina de Fisiología; 2019

Sociedad Argentina de Fisiología

Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of pancreatic cancer and has one of the worse prognosis. The poor overall survival is associated with the overexpression of epidermal growth factor receptor (EGFR), a known member of the ErbB family of receptor tyrosine kinases and multidrug resistance associated protein 4 (MRP4/ABCC4). Our previous results show that high levels MRP4 are associated with increase in tumor cell proliferation, metastatic invasion and up-regulation of EGFR protein levels in PDACs cell lines. The aim of our study was to evaluate the regulation of MRP4 by EGFR activation in a pancreatic cancer cell model. To accomplish our objective, we treated the pancreatic cancer cell line BxPC-3 with EGF (0.1ng/ul). EGFR activation was confirmed by ERK phosphorylation at 5, 10, 20, 30, and 40 min after EGF treatment. MRP4 protein expression was evaluated by western blot using whole cell extracts following incubation with EGF for 0, 24 and 48 h, using histone as loading control. MRP4 expression levels were also assessed 48 h after treatment with EGF alone or in combination with the EGFR inhibitor CL 387-785 (1µM). Our results confirm that EGFR is quickly activated upon incubation with EGF, as evidenced by a 4-fold increase in the pERK/total ERK ratio detected (P