c- fos is required for malignant progression of skin tumors

• Published in: Cell 1995-09, Vol.82 (5), p.721-732
• Main Authors: Saez, Enrique, Rutberg, Susan E, Mueller, Elisabetta, Oppenheim, Heather, Smoluk, Jennifer, Yuspa, Stuart H, Spiegelman, Bruce M
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - genetics; Cell Transformation, Neoplastic - genetics; Epidermal Cells; Gene Expression - physiology; Genes, fos - genetics; Genes, ras - genetics; Keratinocytes - pathology; Keratins - physiology; Mice; Mice, Nude; Mice, Transgenic; Mutation - physiology; Neoplasm Transplantation; Oncogene Protein p21(ras) - genetics; Papilloma - genetics; Papilloma - pathology; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Time Factors; Transcription Factor AP-1 - genetics
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(95)90469-7

The proto-oncogene c-fos is a major nuclear target for signal transduction pathways involved in the regulation of cell growth, differentiation, and transformation. Using the multistep skin carcinogenesis model, we have directly tested the ability of c- fos-deficient mice to develop cancer. Upon treatment with a tumor promoter, c- fos knockout mice carrying a v-H- ras transgene were able to develop benign tumors with similar kinetics and relative incidence as wild-type animals. However, c- fos-deficient papillomas quickly became very dry and hyperkeratinized, taking on an elongated, horny appearance. While wild-type papillomas eventually progressed into malignant tumors, c- fos-deficient tumors failed to undergo malignant conversion. Experiments in which v-H- ras-expressing keratinocytes were grafted onto nude mice suggest that c- fos-deficient cells have an intrinsic defect that hinders tumorigenesis. These results demonstrate that a member of the AP-1 family of transcription factors is required for the development of a malignant tumor.