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Ornithine Decarboxylase Overexpression Is a Sufficient Condition for Tumor Promotion in Mouse Skin¹

The Lankenau Medical Research Center, Wynnewood, Pennsylvania 19096

In multistage tumorigenesis models, ornithine decarboxylase (ODC) is usually dysregulated at some point during tumor promotion, an early stage of carcinogenesis. To address the question whether constitutive overexpression of ODC would be a sufficient condition for tumor promotion, mice with high levels of ODC expression targeted to epidermal keratinocytes were used in skin tumorigenesis experiments. Transgenic mice with ODC targeted to hair follicle keratinocytes were much more sensitive than littermate controls to initiation with a single low dose of carcinogen; in fact, such mice no longer required treatment with tumor promoters for tumors to develop. Targeting ODC overexpression to both interfollicular and follicular keratinocytes did not further enhance tumor yield. Our results suggest that most, if not all, target cells for chemical carcinogens in the skin reside in hair follicles, and ODC overexpression is sufficient to activate such cells to expand clonally to form epidermal tumors.

¹ This work was supported by a NIH Grant ES-01664 (to T. G. O.).

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.

Received 1/13/97. Accepted 5/ 5/97.

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