Dual role of cAMP in the transcriptional regulation of multidrug resistance-associated protein 4 (MRP4) in pancreatic adenocarcinoma cell lines

PloS One
Alejandro CarozzoNatalia Fernández

Abstract

Cyclic AMP represents one of the most studied signaling molecules and its role in proliferation and differentiation processes has been well established. Intracellular cAMP levels are tightly regulated where the MRP4 transporter plays a major role. In the present study, we sought to establish whether cAMP modulated MRP4 expression in pancreatic adenocarcinoma cell lines. Quantitative PCR and western blot studies showed that cAMP-increasing agents enhanced MRP4 transcripts and protein levels in PANC-1 cells. Reporter luciferase experiments carried out in pancreatic AR42J cells showed that intracellular cAMP up-regulates MRP4 through an Epac2- and Rap1-mediated mechanism whereas extracellular cAMP reduced MRP4 promoter activity by a MEK/ERK-mediated pathway. Present results show that cAMP regulates MRP4 promoter activity, and further indicate that the balance between intracellular and extracellular cAMP levels determines MRP4 expression.

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Citations

Jul 8, 2015·The Journal of Pharmacology and Experimental Therapeutics·Jiagen WenWei Zhang
Apr 26, 2020·The FEBS Journal·Angela Rodríguez GonzálezCarina Shayo
Mar 3, 2020·Clinical Pharmacology and Therapeutics·Sanjay K NigamJeremiah D Momper
Mar 12, 2019·Frontiers in Pharmacology·Valeria BurghiFernando P Dominici

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Methods Mentioned

BETA
PCR
Transfection
Assay
GTP
GTPase

Software Mentioned

Genomatrix
Mat Inspector
FlexStation
Genomatrix Suite

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