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Expression Increases Cellular Proliferation, Decreases Differentiation, and Enhances the Transformed Phenotype of CaCo-2 Cells1
Departments of Medicine [B. S-S., C. A., M. B., S. F. S., N. O. D., R. K. W., B. H. D., M. S., T. A. B.] and Pathology [J. H.], the University of Chicago, Chicago, Illinois 60637
Previous studies have shown that PKC-
protein expression is decreased in sporadic human colon cancers, as well as in colonic tumors of rats induced by chemical carcinogens. To elucidate the potential role of PKC- on several phenotypic characteristics of colon cancer cells, we have transfected cDNAs for PKC- in sense or antisense orientations into CaCo-2 cells, a human colonic adenocarcinoma cell line. Transfected clones were isolated that demonstrated 
3-fold increases (sense transfectants) and 95% decreases (antisense transfectants) in PKC- expression with no significant alterations in other PKC isoforms. Transfection of CaCo-2 cells with PKC- in the antisense orientation resulted in enhanced proliferation and decreased differentiation, as well as in a more aggressive transformed phenotype compared with empty vector-transfected control cells. In contrast, cells transfected with PKC- cDNA in the sense orientation demonstrated decreased proliferation, enhanced differentiation, and an attenuated tumor phenotype compared with these control cells. These data show that alterations in the expression of PKC- induce changes in the proliferation, differentiation, and tumorigenicity of CaCo-2 cells. Furthermore, these findings indicate that loss of PKC- expression in sporadic human and chemically induced colonic cancers may confer a relative growth advantage during colonic malignant transformation.
1 This research was supported in part by Grants P30DK42086 (Digestive Diseases Research Core Center; to T. A. B. and N. O. D.), CA36745 (to T. A. B. and M. B.), DK39573 (to T. A. B., M. B., and M. S.), CA69532 (to M. B.), HL-38180 (to N. O. D.), and HL-18577 (to N. O. D.), 5T32DK07074-20 (to B. S. S.) from the USPHS.
2 To whom requests for reprints should be addressed, at Department of Medicine, The University of Chicago Hospitals and Clinics, 5841 South Maryland Avenue, MC4076, Chicago, IL 60637. Phone: (773) 702-9898; Fax: (773) 702-2182; E-mail: tbrasitu@medicine.bsd.uchicago.edu.
Received 9/29/97. Accepted 12/31/97.
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