Antiproliferative effects of interferon alpha on human pancreatic carcinoma cell lines are associated with differential regulation of protein kinase C isoenzymes.

S Rosewicz, M Weder, A Kaiser, E O Riecken

Department of Gastroenterology, Medizinische Klinik and Poliklinik, Khnikum Benjamin Franklin, Berlin, Germany.

BACKGROUND: The molecular mechanisms mediating the antiproliferative effects of interferon alpha on human pancreatic carcinoma cells are poorly understood. AIM: To characterise the effects of interferon alpha on protein kinase C isoenzyme expression in interferon alpha sensitive and resistant human pancreatic tumour cell lines. METHODS: The ductal human pancreatic carcinoma cell lines Capan 1 and Capan 2 were investigated. Anchorage dependent and independent growth was determined by cell number and a human tumour clonogenic assay. Interferon alpha receptor expression was examined by reverse-transcriptase polymerase chain reaction and electrophoretic mobility shift assay. Protein kinase C isoenzyme expression was evaluated by western blotting using monospecific polyclonal antibodies. RESULTS: Interferon alpha treatment results in a time and dose dependent inhibition of anchorage dependent and independent growth in Capan 1 cells while Capan 2 cells were not affected by interferon alpha. Both cell lines express interferon alpha receptor mRNA transcripts. Growth inhibition by interferon alpha in Capan 1 cells was paralleled by a profound decrease of protein kinase C alpha and zeta expression while these isoenzymes were unaffected in the interferon resistant cell line Capan 2. CONCLUSION: Inhibition of protein kinase C isoenzyme expression might determine the sensitivity of a given pancreatic carcinoma to respond to the antiproliferative action of interferon alpha.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Chow, J. Y. C., Dong, H., Quach, K. T., Van Nguyen, P. N., Chen, K., Carethers, J. M. (2008). TGF-{beta} mediates PTEN suppression and cell motility through calcium-dependent PKC-{alpha} activation in pancreatic cancer cells. Am. J. Physiol. Gastrointest. Liver Physiol. 294: G899-G905 [Abstract] [Full Text]  
• Brown, R. E., Lun, M., Prichard, J. W., Blasick, T. M., Zhang, P. L. (2004). Morphoproteomic and Pharmacoproteomic Correlates in Hormone-Receptor-Negative Breast Carcinoma Cell Lines. Annals of Clinical & Laboratory Science 34: 251-262 [Abstract] [Full Text]  
• Brown, R. E., Boyle, J. L. (2003). Mesenchymal Chondrosarcoma: Molecular Characterization by a Proteomic Approach, with Morphogenic and Therapeutic Implications. Annals of Clinical & Laboratory Science 33: 131-141 [Abstract] [Full Text]  
• Guha, S., Rey, O., Rozengurt, E. (2002). Neurotensin Induces Protein Kinase C-dependent Protein Kinase D Activation and DNA Synthesis in Human Pancreatic Carcinoma Cell Line PANC-1. Cancer Res. 62: 1632-1640 [Abstract] [Full Text]  
• Detjen, K M, Farwig, K, Welzel, M, Wiedenmann, B, Rosewicz, S (2001). Interferon {gamma} inhibits growth of human pancreatic carcinoma cells via caspase-1 dependent induction of apoptosis. Gut 49: 251-262 [Abstract] [Full Text]  
• Cook, T., Urrutia, R. (2000). TIEG proteins join the Smads as TGF-beta -regulated transcription factors that control pancreatic cell growth. Am. J. Physiol. Gastrointest. Liver Physiol. 278: G513-G521 [Abstract] [Full Text]  
• Detjen, K., Brembeck, F., Welzel, M, Kaiser, A, Haller, H, Wiedenmann, B, Rosewicz, S (2000). Activation of protein kinase Calpha inhibits growth of pancreatic cancer cells via p21(cip)-mediated G(1) arrest. J. Cell Sci. 113: 3025-3035 [Abstract]