This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Verma, A. K. Search for Related Content PubMed PubMed Citation Articles by Verma, A. K.

The Protein Kinase C Activator L--Dioctanoylglycerol: A Potent Stage II Mouse Skin Tumor Promoter¹

Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison, Wisconsin 53792

Endogenous diacylglycerol, as produced during ligand-stimulated hydrolysis of phosphatidylinositol, is a physiological activator of protein kinase C, a receptor for the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Diacylglycerol mimics many effects of phorbol ester TPA, but it is not known whether diacylglycerol is a mouse skin tumor promoter. The present studies determined the mouse skin tumor-promoting activity of L--dioctanoylglycerol (DG), a membrane-permeable diacylglycerol derivative. In two independent experiments with female SENCAR mice, DG at a 2 µmol dose, when applied twice weekly to the initiated mouse skin, failed to promote mouse skin tumor formation. Similarly, DG lacked Stage I tumor-promoting activity; twice weekly applications of DG for 2 wk to the initiated mouse skin followed by twice weekly applications of mezerein (3.3 nmol) for as long as 27 wk elicited only a few papillomas per mouse. DG was found to be a potent Stage II mouse skin tumor promoter. In a typical two-stage tumor promotion experiment, SENCAR mice were initiated by application of 20 nmol of DMBA to their shaved backs. Two wk after initiation, 3.3 nmol of TPA were applied twice weekly for 2 wk (Stage I), and then 2 µmol of DG or 3.3 nmol of mezerein were applied to the skin twice weekly for the entire duration of the experiment (Stage II). Stage II tumor promotion with mezerein and DG resulted in 13.33 ± 0.88 and 11.13 ± 1.25 papillomas per mouse, respectively, at 19 wk and the carcinoma incidence, 43% and 33%, respectively, at 27 wk of promotion. The tumor-promoting activity of DG was compared with the parent alcohol glycerol, and it was found that glycerol, at a dose as high as 11 µmol, was not a complete, Stage I or Stage II mouse skin tumor promoter. Both TPA and DG, when applied to mouse skin, induced epidermal ornithine decarboxylase activity. Both TPA and DG activate protein kinase C, but the results presented indicate that TPA and DG differ in their tumor-promoting properties. DG, like mezerein, is a Stage II mouse skin tumor promoter.

¹ The work was supported by USPHS Grant CA 35368 from the NIH.

² To whom requests for reprints should be addressed.

Received 9/ 8/87. Revised 12/ 2/87. Accepted 12/16/87.

This article has been cited by other articles:

				M. Gartsbein, A. Alt, K. Hashimoto, K. Nakajima, T. Kuroki, and T. Tennenbaum The role of protein kinase C {delta} activation and STAT3 Ser727 phosphorylation in insulin-induced keratinocyte proliferation J. Cell Sci., February 1, 2006; 119(3): 470 - 481. [Abstract] [Full Text] [PDF]

				P. J. Reddig, N. E. Dreckschimdt, H. Ahrens, R. Simsiman, C.-P. Tseng, J. Zou, T. D. Oberley, and A. K. Verma Transgenic Mice Overexpressing Protein Kinase C{{delta}} in the Epidermis Are Resistant to Skin Tumor Promotion by 12-O-Tetradecanoylphorbol-13-acetate Cancer Res., November 1, 1999; 59(22): 5710 - 5718. [Abstract] [Full Text] [PDF]