STRUCTURAL AND FUNCTIONAL PROPERTIES OF ADENYLYL CYCLASE-ASSOCIATED PROTEIN 1/ADENYLYL CYCLASE COMPLEXES IN PANCREATIC CANCER CELLS

Abstract

Of all the different cancers, pancreatic cancer is one of the major unsolved health problems. It is important to study the mechanism through which the pancreatic cells migrate to prolong survival in patients. Concerning the progression of pancreatic cancer, the adenylyl cyclase (AC)/adenosine 3�,5� cyclic monophosphate (cyclic AMP) pathway has shown to inhibit in the migration of pancreatic cancer cells. �Adenylyl cyclase- associated protein 1 (CAP1) is a protein that is involved in the regulation of actin microfilament formation, which ultimately leads to cell migration and invasion. The CAP 1 protein binds to G-actin, inhibiting polymerization which inhibits filopodia formation, inhibiting cell migration. In a previous research project in the lab it was found that CAP 1 reacts with different adenylyl cyclase (AC) isoforms: AC1, AC3, AC4 and AC7. behavior. The objective of this research was, through theoretical and experimental analyses, to determine to which extent CAP1 interacts with the 4 transmembrane AC isoforms mentioned above.�Through a sequential co-immunoprecipitation approach, I determined which AC isoform experimentally has a higher affinity for CAP1 using the HPAC cell line, which is moderately differentiated. Based on the theoretical and experimental results, AC3 and AC4 have the highest affinity for CAP1.