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

ANA SAHORES; CAROLINA GHANEM; RODRIGO LAGOS; JULIETA IMPERIALE; ISMAEL BARROSO; CARLOS DAVIO

Rosario, Santa Fe

Congreso; SAFIS; 2019

SAFIS

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, among others, to the overexpression of epidermal growth factor receptor (EGFR), a known member of the ErbB family of receptor tyrosine kinases. Our previous results show that high levels of multidrug resistance associated protein 4 (MRP4/ABCC4) are associated to an increase in tumor cell proliferation, metastatic invasion and poor prognosis in PDAC patients. MRP4 is responsible for substance extrusion, including cAMP and PGE2. The aim of our study was to evaluate MRP4 regulation by EGFR activation in a pancreatic cancer model. To accomplish our objective, we treated the pancreatic cancer cell line BxPC-3 with EGF (0.1ng/ul). The activation of EGFR was confirmed by ERK phosphorylation at 5, 10, 20, 30, and 40 minutes. MRP4 protein expression was evaluated by western blot of whole extracts of these cells after incubation for 0, 24 and 48 hours with EGF, using histone as housekeeping. MRP4 expression levels were also assessed 48 hours after treatment with EGF alone or in combination with CL 387-785 (EGFR inhibitor, 1µM). Our results confirm that EGFR is quickly activated upon incubation with EGF, as a 4.12 fold increase in the pERK/totalERK ratio was detected (P