Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent cancer of the pancreas with a 5-year survival rate of 9%, making it the 3rd most common cause of cancer deaths in the United States. One of the challenges related to this cancer is the issue of chemoresistance. Chemoresistance renders most drugs ineffective in the treatment of PDAC, including kinase inhibitors and chemotherapy. PIM (Proviral Integration site for the Moloney murine leukemia virus) kinases are a family of oncogenic proteins shown to play an important role in the chemoresistance of many cancers, including pancreatic cancer. PIMs act downstream of the JAK-STAT cytokine signaling pathway and phosphorylate substrates involved in numerous cell functions including cell cycle progression and apoptosis. To determine the role of PIM kinases on transformed phenotypes of PDAC cells, we tested shRNAs and kinase inhibitors made against PIM kinases. We were able to demonstrate that PIM kinase inhibition was able to decrease transformed phenotypes such as anchorage-dependent and anchorage-independent growth in the PDAC cells. Also, we observed that PIM inhibition was able to sensitize PDAC cells to chemotherapy. Overall, our results suggest that PIM kinases are an important molecular target for cell growth and chemoresistance in pancreatic cancer.
Antonio T. Baines, Ph.D.
Department of Biological & Biomedical Sciences
Cancer Research Program
Director, Integrated Biosciences Ph.D. Program
North Carolina Central University
367 College of Medicine East Tower
Lectures, Seminars and Meetings
UI Cancer Center Cancer Biology Program