The Lack of AC1 Impairs the Inhibitory Effects of cAMP on Cell Mitigation and Proliferation in Pancreatic Cancer

Abstract

Introduction: Adenylyl cyclase (AC) is an important enzyme in signal transduction processes. This protein catalyzes the conversion of ATP to cAMP. We found five isoforms of AC in human pancreatic carcinoma HPAC cell line: AC1, AC3, AC6, AC7 and AC9. Both AC1 and AC3 are very important because they are up-regulated in HPAC cells. We also found that forskolin (FSK}, inhibits cell proliferation and cell migration but not cell invasion in HPAC cells. Objective: To silence AC1 and AC3 and determine their participation in the inhibitory effect of cAMP on cell migration and proliferation of HPAC cells. Results: To study the functional roles of AC1 and AC3, the expression of both isoforms were knocked-out using siRNA (human). The lack of either AC1 or AC3 proteins was assessed using Western-blotting. When testing for cell proliferation and cell migration, we found that the inhibitory effect of FSK was impaired in the presence of siRNA AC1, but not in the presence of siRNA AC3. Discussion: We conclude that AC1 mediates the inhibitory effect of cAMP in cell proliferation and migration. Begin Time: 26:09 End Time: 44:52