Abstract
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, α-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.
Footnotes
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↵1 Supported in part by Grant ES01664 from the NIH, Department of Health and Human Services.
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↵2 To whom requests for reprints should be addressed, at The Lankenau Medical Research Center, 100 Lancaster Avenue, Wynnewood, PA 19096. Phone: (610) 645-3507; Fax: (610) 645-3561; E-mail: obrient@alhs.org.
- Received November 10, 1997.
- Accepted February 18, 1998.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 8
