The study demonstrated that elevated levels of ornithine decarboxylase (ODC) and polyamines, when combined with a mutant Ha-ras gene, led to spontaneous tumor development in double transgenic mice. These mice, which were bred to carry both K6/ODC and v-Ha-ras transgenes, developed well-differentiated keratoacanthomas, some of which progressed to carcinomas within 2 months. The tumor development was dependent on ODC, as the use of the ODC inhibitor DFMO prevented tumor formation and caused regression. This indicated that ODC overexpression and activated Ha-ras were sufficient for malignant transformation, providing a model to study epithelial tumor development without chemical carcinogens or tumor promoters.
233 citations,
July 1997 in “PubMed” In this study, researchers investigated whether overexpression of ornithine decarboxylase (ODC) was sufficient for tumor promotion in mouse skin. They used transgenic mice with high ODC expression in epidermal keratinocytes and found that these mice were more sensitive to carcinogen initiation compared to controls. Notably, mice with ODC overexpression in hair follicle keratinocytes developed tumors without the need for additional tumor promoters. The study concluded that ODC overexpression was sufficient to activate target cells in hair follicles, leading to clonal expansion and epidermal tumor formation, indicating that hair follicles are key sites for chemical carcinogen targeting in the skin.
37 citations,
January 1986 in “Carcinogenesis” The study investigated the expression of ornithine decarboxylase (ODC) in mouse skin treated with the tumor promoter TPA. It was found that ODC expression was heterogeneous, with high levels predominantly in suprabasal cells around hair follicles shortly after TPA treatment. This expression was transient, disappearing within 16 to 24 hours, but persisted in some cells within benign papillomas a week after TPA application. Pretreatment with retinoic acid or cycloheximide inhibited ODC expression. The findings suggested that both normal and tumor tissues in mice exhibited varied ODC expression.
