Protein Kinase C Alpha (PKCα) Regulates Growth and Invasion of Endometrial Cancer Cells

The etiology of endometrial cancers remains poorly understood, particularly with respect to signal transduction pathways underlying the development and progression of the more aggressive, type II steroid-independent tumors. Protein kinase C alpha (PKC alpha) regulates cellular processes critical to malignancy and has been implicated in the pathogenesis of endometrial cancers. The objective of these studies was to determine the functional role of PKC alpha in endometrial cancer cell proliferation, anchorage-independent growth, and invasion. PKC alpha expression in endometrial cancer cell lines was examined by Western blotting. PKC alpha levels were increased in type II HEC-50, HEC-1-A and HEC-1-B cell lines relative to the type I Ishikawa and RL-95-2 lines. Retroviral constructs were used to either overexpress PKC alpha or selectively knockdown levels by shRNA in Ishikawa and HEC 50 cells, respectively. Knockdown of PKC alpha expression in HEC-50 cells resulted in a diminished growth rate and attenuation of anchorage-independent growth. Correspondingly, Ishikawa cells overexpressing PKC alpha protein exhibited increased proliferation, resistance to growth factor deprivation and enhanced anchorage-independent growth. Consistent with the observed changes in cell proliferation, PKC alpha also modulated cyclin D1 promoter activity in both cell lines. A reduction in PKC alpha levels rendered HEC-50 cells significantly less invasive, whereas PKC alpha overexpression enhanced invasion of Ishikawa cells. These data indicate that PKC alpha promotes growth and invasion of endometrial cancer cells, suggesting that PKC alpha dependent signaling pathways could provide novel prognostic indicators or therapeutic targets, particularly in clinically aggressive type II endometrial tumors. J. Cell. Physiol. 220: 112-118, 2009. (C) 2009 Wiley-Liss, Inc.