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Molecular Mechanisms of Mouse Skin Tumor Promotion
The University of Texas M. D. Anderson Cancer Center, Science Park–Research Division, P.O. Box 389, Smithville, TX 78957, USA
* Author to whom correspondence should be addressed.
Received: 4 March 2010; in revised form: 26 March 2010 / Accepted: 7 April 2010 / Published: 13 April 2010
Abstract: Multiple molecular mechanisms are involved in the promotion of skin carcinogenesis. Induction of sustained proliferation and epidermal hyperplasia by direct activation of mitotic signaling pathways or indirectly in response to chronic wounding and/or inflammation, or due to a block in terminal differentiation or resistance to apoptosis is necessary to allow clonal expansion of initiated cells with DNA mutations to form skin tumors. The mitotic pathways include activation of epidermal growth factor receptor and Ras/Raf/mitogen-activated protein kinase signaling. Chronic inflammation results in inflammatory cell secretion of growth factors and cytokines such as tumor necrosis factor-α and interleukins, as well as production of reactive oxygen species, all of which can stimulate proliferation. Persistent activation of these pathways leads to tumor promotion.
Keywords: skin carcinogenesis; tumor promoters; 12-O-tetradecanoylphorbol 13-acetate (TPA); protein kinase C (PKC); epidermal growth factor receptor (EGFR); transforming growth factor-β (TGFβ); tumor necrosis factor-α (TNFα); interleukins; cyclooxygenase-2 (COX-2); ornithine decarboxylase (ODC)
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Rundhaug, J.E.; Fischer, S.M. Molecular Mechanisms of Mouse Skin Tumor Promotion. Cancers 2010, 2, 436-482.
Rundhaug JE, Fischer SM. Molecular Mechanisms of Mouse Skin Tumor Promotion. Cancers. 2010; 2(2):436-482.
Rundhaug, Joyce E.; Fischer, Susan M. 2010. "Molecular Mechanisms of Mouse Skin Tumor Promotion." Cancers 2, no. 2: 436-482.