Modified from Hruban et al. (2000) Artwork by Jennifer Parsons-Brumbaugh
Pancreatic cancer is the 4th most common cause of cancer deaths in the United States. Due to the aggressive nature of this cancer and the lack of biomarkers for early detection, the incidence and mortality rates for pancreatic cancer are nearly equivalent. The presence of oncogenically mutated K-Ras in 90% of human pancreatic ductal adenocarcinomas (PDAC) strongly suggests a critical role for this genetic mutation in the development of this disease. Despite intensive effort, disappointingly, to date no anti-Ras therapies have successfully reached the clinic.
The overall focus of our cancer biology research program is to identify and validate the role of novel molecular targets in the development and progression of normal cells transforming into cancer cells of the pancreas. A recent study identified upregulation of the Pim-1 serine/threonine kinase in Ras-mediated transformation of human pancreatic ductal epithelial cells. A second study identified upregulation of the related Pim-3 in PDAC cell lines and patient samples. We hypothesize that inhibition of Pim function will be an effective approach for antagonizing the aberrant growth of pancreatic carcinoma. To test this hypothesis, we will determine the contribution of upregulated Pim kinase genes in aberrant growth transformation of pancreatic cancer. Results from these studies will allow us to critically validate these kinases as novel therapeutic targets for PDAC treatment.
- Dr. Dapeng Xu
- Dr. Vijaya Nandiwada
- Michael Cobb
- Dana Austin
- Naima Stennett
- Aurora Baker
- Kala Nwachukwu
- Preston Newby
Publications by Antonio T Baines
Xu, D., Allsop, S., Witherspoon, S.M., Snider, J.L., Yeh, J.J., Fiordalisi, J.J., White, C.D., Williams, D., Cox, A.D., and Baines, A.T. (2011) The oncogenic kinase Pim-1 is modulated by K-Ras signaling and mediates transformed growth and radioresistance in human pancreatic ductal adenocarcinoma cells. Carcinogenesis, 32:4, 488-495.
Rybarczyk, B. J., Baines, A.T., McVey, M., Thompson, J.T., and Wilkins, H. "A Case-based Approach Increases Student Learning Outcomes and Comprehension of Cellular Respiration Concepts", Biochemistry and Molecular Biology Education, Vol. 35, No. 3, pp. 181 -186, 2007.
Lim, K.-H., Baines, A.T., Fiordalisi, J.J., Shipitsin, M., Feig, L.A., Cox, A.D., Der, C.J., and Counter, C.M.: Activation of RalA is critical for Ras-induced tumorigenesis of human cells. Cancer Cell 7:533-545, 2005.
Baines, A.T., Lim, K.-H., Shields, J.M., Lambert, J.M., Counter, C.M., Der, C.J., and Cox, A.D.: Use of retrovirus expression of interfering RNA to determine the contribution of activated K-Ras and Ras effector expression in human tumor cell growth. Methods in Enzymology. Vol. 407, pp. 556-74, 2005.
Baines, A., Taylor-Parker, M., Goulet, A.-C., Renaud, C., Gerner, E.W., and Nelson, M.A.: Selenomethionine inhibits growth and suppresses cyclooxygenase-2 (COX-2) protein expression in human colon cancer cell lines.Cancer Biology and Therapy1(4):370-4, 2002.