Effectors Implicated In the Ac1 Inhibitory Effect on Cell Proliferation in Pancreatic Cancer Cells

Abstract

Introduction and aim: Pancreatic adenocarcinoma is among the most aggressive of all cancers. Adenosine 3’, 5’ cyclic monophosphate (cyclic AMP) is involved in the internal cellular enzymatic activity and gene expression. It is found to be involved in the mechanism of pancreatic tumorigenesis. So far, two effectors for cyclic AMP are known; one is protein kinase A (PKA) and the other is an exchange protein directly activated by cAMP (EPAC). Our research group has found that AC1 is responsible for the inhibitory effect of Forskolin on cell proliferation of HPAC. My research project focuses on studying the effectors implicated in the inhibitory effect of activated AC1. Result: We were successfully able to overexpress AC1 using a plasmid human ADCY1 cDNA in pCMV-SPORT6. Through the overexpression, we were able to support the conclusion that AC1 inhibits cell proliferation in HPAC cells. We found that both H-89 (inhibitor of PKA) and ESI (inhibitor of EPAC) counteracts the effect of AC1. Conclusion: Both effectors- PKA and EPAC- mediate the inhibitory effect of AC1. Funding Source: Center for Undergraduate Research and Scholarship and Department of Biological Sciences, Scholarly Activity Award