This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Verma, A. K. Articles by Erickson, D. Search for Related Content PubMed PubMed Citation Articles by Verma, A. K. Articles by Erickson, D.

Involvement of Protein Kinase C Activation in Ornithine Decarboxylase Gene Expression in Primary Culture of Newborn Mouse Epidermal Cells and in Skin Tumor Promotion by 12-O-Tetradecanoylphorbol-13-acetate¹

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

The role of protein kinase C in ornithine decarboxylase (ODC; EC 4.1.1.17) gene expression in primary culture of newborn mouse epidermal cells (MEC) from BALB/c mice and in skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in female CD-1 mice was determined. A time course and the dose-response curves of ODC induction paralleled that of ODC mRNA induction by TPA in MEC. TPA treatment did not elicit any change in the size of ODC mRNA. The magnitude of ODC induction was proportional to the amount of ODC mRNA increased by TPA. TPA (2 x 10^-7 M) failed to induce ODC activity in MEC plated in Ca²⁺-deprived medium; TPA induction of ODC could be resumed upon Ca²⁺ restoration in the medium. 1-Oleoyl-2-acetylglycerol, a membrane-permeable diacylglycerol which activates protein kinase C, induced at the same rate both ODC activity and the amount of ODC mRNA in MEC. Phospholipase C, which releases diacylglycerol from membrane phospholipids, also induced ODC activity; 0.02 units of phospholipase C per ml led to about a 50-fold increase in ODC activity at 6 h after treatment. Phospholipase A₂ was ineffective. Phospholipase C-induced ODC activity correlated with an increased level of ODC mRNA. Furthermore, palmitoylcarnitine, an inhibitor of protein kinase C, inhibited epidermal ODC induction and the increased level of ODC mRNA by TPA. Also, palmitoylcarnitine inhibited skin tumor promotion by TPA; application of 3 µmol of palmitoylcarnitine in conjunction with each promotional treatment with 10 nmol of TPA to the initiated skin of female CD-1 mice inhibited tumor formation. Taken together, we conclude that activation of protein kinase C may be an early event in ODC gene transcription and skin tumor promotion by TPA.

¹ The work was supported by USPHS Research Grant CA-35368 from the National Cancer Institute. A preliminary report of this work was presented at the 77th Annual Meeting of the American Association for Cancer Research, Inc. (57).

² To whom requests for reprints should be addressed.

Received 6/ 9/86. Revised 9/ 3/86. Accepted 9/ 5/86.

This article has been cited by other articles:

				S. K. Lee, W. G. Qing, W. Mar, L. Luyengi, R. G. Mehta, K. Kawanishi, H. H. S. Fong, C. W. W. Beecher, A. D. Kinghorn, and J. M. Pezzuto Angoline and Chelerythrine, Benzophenanthridine Alkaloids That Do Not Inhibit Protein Kinase C J. Biol. Chem., July 31, 1998; 273(31): 19829 - 19833. [Abstract] [Full Text] [PDF]

				J. G. Guillem, C. A. O'Brian, C. J. Fitzer, M. D. Johnson, K. A. Forde, P. LoGerfo, and I. B. Weinstein Studies on Protein Kinase C and Colon Carcinogenesis Arch Surg, December 1, 1987; 122(12): 1475 - 1478. [Abstract] [PDF]