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Evidence against a role of general protein kinase C downregulation in skin tumor promotion
Author(s) -
Manzow Simone,
Richter Karl Hartmut,
Stempka Luise,
Fürstenberger Gerhard,
Marks Friedrich
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000215)85:4<503::aid-ijc10>3.0.co;2-l
Subject(s) - protein kinase c , tumor promotion , downregulation and upregulation , epidermis (zoology) , isozyme , immune system , gene isoform , biology , cancer research , immunology , microbiology and biotechnology , chemistry , signal transduction , endocrinology , medicine , enzyme , biochemistry , cancer , anatomy , carcinogenesis , gene
Using isoenzyme‐specific antibodies, we have performed an immunoblot analysis of the PKC isoenzyme pattern during the course of TPA‐induced tumor promotion in the epidermis of NMRI mice. The TPA‐sensitive PKC isoforms α, δ, ϵ, η, μ (and TPA‐insensitive PKCζ), but not PKCβ and γ, were found to be expressed in both normal and neoplastic epidermis. The immune signals of all TPA‐sensitive PKC isoforms were moderately and reversibly attenuated upon a single TPA treatment. Using different antibodies against PKCη and PKCμ, this apparent downregulation could mainly be attributed to epitope changes of these enzymes, whereas for the other PKC species no such conclusion could be drawn. Except for PKCϵ, no substantial long‐term attenuation of the immune signals of the other PKC isoforms occurred upon chronic phorbol ester treatment ( i.e., 14 applications of 5 nmol TPA each over 7 weeks), which led to tumor development in initiated mouse skin. Specific PKC activity (related to tissue weight) was 40–50% lower in TPA‐treated as compared with control epidermis whereby no clearcut difference was found between single and chronic TPA treatment. Benign and malignant skin tumors generated according to the initiation‐promotion protocol did not exhibit consistent alterations in the immune pattern of the PKC isoenzymes with the exception of a decrease of PKCϵ and an increase of PKCμ signal in carcinomas. Our data indicate that, in contrast with earlier assumptions, no general long‐lasting PKC downregulation plays a critical role in skin tumor promotion. Int. J. Cancer 85:503–507, 2000. © 2000 Wiley‐Liss, Inc.