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Superinduction of mouse epidermal ornithine decarboxylase activity by repeated 12-0-tetradecanoylphorbol-13-acetate treatments

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Abstract

A correlation of the levels of epidermal protein kinase C (PKC) isozymes, steady state levels of ornithine decarboxylase (ODC) mRNA, and ODC antizyme with the induction of ornithine decarboxylase (ODC) activity by a second repeat 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment to mouse skin was determined. A single application of TPA to female CD-1 mouse skin leads to a dramatic induction of ODC activity (≈3 nmol CO2/60 min/mg protein) which peaks at about 5 h after treatment. However, a superinduction of ODC activity (≈13 CO2/60 min/mg protein) is observed upon the second TPA application at 48 or 72 h after the first TPA treatment. Prior application of a tumor initiating dose of 7,12-dimethylbenz[a]anthracine to mouse skin did not influence the degree of induction of ODC by a repeat TPA treatment. Western Blot analyses using antibodies specific to PKC α, β, γ, ɛ and s indicate detectable levels of PKC α, β, δ and ε in mouse epidermal extracts. A time course of the effects of a single topical application of 20 nmol of TPA to the mouse skin indicate that none of PKC isozymes (α, β, γ, δ and ɛ) were completely downregulated at times (72 h) when ODC was overinduced by TPA. TPA-induced steady state levels of ODC mRNA did not correlate with the degree of superinduction of ODC activity by TPA. The second TPA treatment, 72 h after the first TPA treatment, which leads to superinduction of ODC activity did not decrease the levels of the ODC-antizyme. The results indicate that superinduction of mouse epidermal ODC activity is regulated in part post-transcriptionally and may not be the result of either a loss of PKC isoform(s) or a decrease in the levels of ODC antizyme.

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Abbreviations

TPA:

12-0-tetradecanoylphorbol-l3-acetate

PKC:

protein kinase C

ODC:

ornithine decarboxylase

IPTG:

Isopropyl β-D-thiogalactopyranoside

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Authors and Affiliations

  1. Department of Human Oncology, Medical School, University of Wisconsin Comprehensive Cancer Center, USA

    A.K. Verma, K.M. Hsiao & H. Ahrens

  2. National Cancer Research Institute, Jikei University School of Medicine, Tokyo, Japan

    M. Suganuma & H. Fujiki

  3. Jikei University School of Medicine, Tokyo, Japan

    S. Matsufuji & H. Hayashi

Authors
  1. A.K. Verma
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  2. K.M. Hsiao
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  3. H. Ahrens
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  4. M. Suganuma
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  5. H. Fujiki
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  6. S. Matsufuji
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  7. H. Hayashi
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The work was supported by the USPHS grant CA35368 from the National Institute of Health.

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Verma, A., Hsiao, K., Ahrens, H. et al. Superinduction of mouse epidermal ornithine decarboxylase activity by repeated 12-0-tetradecanoylphorbol-13-acetate treatments. Mol Cell Biochem 155, 139–151 (1996). https://doi.org/10.1007/BF00229311

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  • DOI: https://doi.org/10.1007/BF00229311

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