c-Fos is required for malignant progression of skin tumors

E Saez, SE Rutberg, E Mueller, H Oppenheim… - Cell, 1995 - cell.com
E Saez, SE Rutberg, E Mueller, H Oppenheim, J Smoluk, SH Yuspa, BM Spiegelman
Cell, 1995cell.com
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-los-deficient
mice to develop cancer. Upon treatment with a tumor promoter, c-los knockout mice carrying
a vH-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 …
Summary
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-los-deficient mice to develop cancer. Upon treatment with a tumor promoter, c-los knockout mice carrying a vH-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-los-deficient tumors failed to undergo malignant conversion. Experiments in which vH-ras-expressing keratinocytes were grafted onto nude mice suggest that c-los-defi-cient 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.
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