title: Protein kinase C alpha (PKCalpha) regulates growth and invasion of endometrial cancer cells.
abstract: 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 (PKCalpha) 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 PKCalpha in endometrial cancer cell proliferation, anchorage-independent growth, and invasion. PKCalpha expression in endometrial cancer cell lines was examined by Western blotting. PKCalpha 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 PKCalpha or selectively knockdown levels by shRNA in Ishikawa and HEC 50 cells, respectively. Knockdown of PKCalpha expression in HEC-50 cells resulted in a diminished growth rate and attenuation of anchorage-independent growth. Correspondingly, Ishikawa cells overexpressing PKCalpha protein exhibited increased proliferation, resistance to growth factor deprivation and enhanced anchorage-independent growth. Consistent with the observed changes in cell proliferation, PKCalpha also modulated cyclin D1 promoter activity in both cell lines. A reduction in PKCalpha levels rendered HEC-50 cells significantly less invasive, whereas PKCalpha overexpression enhanced invasion of Ishikawa cells. These data indicate that PKCalpha promotes growth and invasion of endometrial cancer cells, suggesting that PKCalpha dependent signaling pathways could provide novel prognostic indicators or therapeutic targets, particularly in clinically aggressive type II endometrial tumors.
authors.affiliation: Division of Basic Reproductive Science, Department of Obstetrics and Gynecology, University of Colorado Denver School of Medicine Aurora, Colorado 80045, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Haughian
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Bradford
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011817:Rabbits; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C530104:CCND1 protein, human; D034741:RNA, Small Interfering; D019938:Cyclin D1; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha