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Publication : Polyamines regulate expression of the neoplastic phenotype in mouse skin.

First Author  Peralta Soler A Year  1998
Journal  Cancer Res Volume  58
Issue  8 Pages  1654-9
PubMed ID  9563478 Mgi Jnum  J:47024
Mgi Id  MGI:1202505 Citation  Peralta Soler A, et al. (1998) Polyamines regulate expression of the neoplastic phenotype in mouse skin. Cancer Res 58(8):1654-9
abstractText  Elevated polyamine levels are characteristic of many types of neoplastic cells and tissues. We demonstrate that in transgenic mice overexpressing ornithine decarboxylase in skin, changes in tissue polyamine levels, particularly putrescine, control the development and maintenance of the neoplastic phenotype. A specific inhibitor of the transgene, alpha-difluoromethylornithine (DFMO), reversibly blocked the appearance of squamous papillomas after carcinogen treatment. Furthermore, treatment of papilloma-bearing mice with DFMO caused rapid tumor regression, also in a reversible manner. Although the rate of apoptosis in papillomas was unaffected by acute DFMO treatment, tumor cell proliferation was rapidly decreased after drug treatment. Conversely, proliferation of normal epidermal keratinocytes was unaffected by DFMO treatment. The regulatory polyamine in this model appears to be putrescine, the immediate product of ornithine decarboxylase. These results demonstrate that elevated polyamine levels are required for both the development and maintenance of the neoplastic phenotype in skin.
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