MRP4 as an oncogene in pancreatic cancer: overexpression of MRP4 induces cell proliferation, tumor growth and chemoresistance

MARTÍN ABBA; MARÍA MAY; ANA SAHORES; CARINA SHAYO ; ANGELA RODRÍGUEZ-GONZÁLEZ ; NICOLÁS DI SIERVI; CARLOS DAVIO; AGUSTÍN YANEFF; GONZALO R. SEQUEIRA

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAIC, SAIB, SAB, etc

Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer-related deaths worldwide; due to its late diagnosis, high resistance to chemotherapy and early onset of metastasis. Even after the emergence of new targeted agents and the possibility of therapeutic combinations, no differences in overall survival are actually seen. Thus, there is an urgent need of novel therapeutic strategies to target PDAC. MRP4 transports endogenous and exogenous substances and its deregulation has been reported in numerous types of cancers. Recent evidence from our lab shows that the activity of MRP4, mainly the efflux of AMPc, is critical for PDAC cell proliferation and that its inhibition causes a clear decrease in malignancy and invasive capacity, suggesting MRP4 as an attractive therapeutic target. The aim of this study was to investigate the role of MRP4 in pancreatic cancer progression and chemoresistance. We used the BxPC-3 pancreatic cell line to establish two clones which overexpress MRP4 significantly (G6 and H7) compared to the control cell line (C4). Western blot and qPCR assays confirmed higher MRP4 protein and mRNA levels, respectively. MRP4 overexpression confers a higher proliferative rate and lower duplication time (p