This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lamm, M. L. G. Articles by Lee, C. Search for Related Content PubMed PubMed Citation Articles by Lamm, M. L. G. Articles by Lee, C.

Transforming Growth Factor-ß1 Inhibits Membrane Association of Protein Kinase C in a Human Prostate Cancer Cell Line, PC3¹

Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611

Address all correspondence and requests for reprints to: Marilyn L. G. Lamm, Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611. E-mail: mlamm{at}nwu.edu

The postreceptor signaling pathway(s) that mediates the effects of transforming growth factor-ß1 (TGF-ß1) is incompletely understood. The present study investigated the involvement of protein kinase C (PKC) in the growth-inhibitory action of TGF-ß1 in PC3, a human prostate cancer cell line. PKC, the only conventional PKC isoform detected in PC3 cells, appeared to be constitutively active based on its presence in both Triton-soluble membrane fraction and cytosol. However, levels of membrane-associated PKC were decreased by a growth-inhibitory dose of TGF-ß1. The response to TGF-ß1 was rapid (within 5 min), time dependent, isoform specific, and occurred without apparent changes in levels of total PKC protein. TGF-ß1 also decreased the levels of membrane-associated PKC activity coincident with its inhibitory effect on PKC’s membrane association. Inhibition of PKC activity appeared to be associated with growth inhibition in PC3 cells, because chelerythrine (a specific PKC inhibitor) likewise decreased cell proliferation. Taken together, our data suggest that inhibition of PKC activity, at least in part due to inactivation of PKC, is an early event associated with TGF-ß1 postreceptor signaling that might mediate suppression of cell proliferation.

This article has been cited by other articles:

				L. Fan, C. V. Pepicelli, C. C. Dibble, W. Catbagan, J. L. Zarycki, R. Laciak, J. Gipp, A. Shaw, M. L. G. Lamm, A. Munoz, et al. Hedgehog Signaling Promotes Prostate Xenograft Tumor Growth Endocrinology, August 1, 2004; 145(8): 3961 - 3970. [Abstract] [Full Text] [PDF]

				A. W. Tolcher, L. Reyno, P. M. Venner, S. D. Ernst, M. Moore, R. S. Geary, K. Chi, S. Hall, W. Walsh, A. Dorr, et al. A Randomized Phase II and Pharmacokinetic Study of the Antisense Oligonucleotides ISIS 3521 and ISIS 5132 in Patients with Hormone-refractory Prostate Cancer Clin. Cancer Res., August 1, 2002; 8(8): 2530 - 2535. [Abstract] [Full Text] [PDF]

				P. Cornford, J. Evans, A. Dodson, K. Parsons, A. Woolfenden, J. Neoptolemos, and C. S. Foster Protein Kinase C Isoenzyme Patterns Characteristically Modulated in Early Prostate Cancer Am. J. Pathol., January 1, 1999; 154(1): 137 - 144. [Abstract] [Full Text] [PDF]