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Protein kinase Cδ-mediated signal to ornithine decarboxylase induction is independent of skin tumor suppression

Oncogene volume 21, pages 3620–3630 (2002)Cite this article

Abstract

Protein Kinase Cδ (PKCδ), a Ca2+-independent, phospholipid-dependent serine/threonine kinase, is among the PKC isoforms expressed in mouse epidermis. We reported that FVB/N transgenic mice that overexpress (∼ eightfold) PKCδ protein in basal epidermal cells are resistant to skin tumor formation by the 7,12-dimethylbenz(a)anthracene (DMBA)-initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promotion protocol. However, despite being resistant to skin tumor promotion by TPA, PKCδ transgenic mice elicited a 3–4-fold increase in TPA-induced epidermal ODC activity and putrescine levels than their wild-type littermates. PKCδ was observed to be the key component of the TPA signal transduction pathways to the induction of mouse epidermal ODC activity. To determine if TPA-induced ODC activity and associated putrescine levels in PKCδ transgenic mice contributed to PKCδ-mediated suppression of skin tumor promotion by TPA, the irreversible inhibitor of ODC, α-difluoromethylornithine (DFMO), was used. PKCδ transgenic mice and their wild-type littermates were initiated with 100 nmol DMBA and then promoted twice weekly with 5 nmol TPA. The experimental group was given 0.5% DFMO in their drinking water, while the control group was given tap water. After 25 weeks, the number of papillomas (>2 mm) per mouse was counted. The DFMO treatment did not affect the skin tumor multiplicity of PKCδ transgenic mice. These results indicate that PKCδ-induced ODC activity is not involved in PKCδ-mediated tumor suppression. Thus, the signaling pathways via PKCδ to epidermal ODC induction and skin tumor suppression appear to be independent.

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Abbreviations

TPA:

12-O-tetradecanoylphorbol-13-acetate

PKC:

protein kinase C

DMBA:

7,12-dimethylbenz[a]anthracine

DFMO:

α-difluoromethylornithine

ODC:

ornithine decarboxylase

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Authors and Affiliations

  1. Department of Human Oncology, Medical School, University of Wisconsin, Madison, 53792, Wisconsin, WI, USA

    Deric L Wheeler, Nancy E Dreckschmidt & Ajit K Verma

  2. Department of Pharmacology, University of North Carolina, Chapel Hill, 27599, North Carolina, NC, USA

    Peter J Reddig

  3. Max-Planck Institute for Experimental Endocrinology, Feodor-Lynen-Str.7, Hanover, 30625, Germany

    Michael Leitges

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  1. Deric L Wheeler
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  2. Peter J Reddig
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  4. Michael Leitges
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  5. Ajit K Verma
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Correspondence to Ajit K Verma.

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Wheeler, D., Reddig, P., Dreckschmidt, N. et al. Protein kinase Cδ-mediated signal to ornithine decarboxylase induction is independent of skin tumor suppression. Oncogene 21, 3620–3630 (2002). https://doi.org/10.1038/sj.onc.1205451

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