Androgen Receptor Actions Modify Skin Structure and Chemical Carcinogen-Induced Skin Cancer Susceptibility in Mice

January 2015 in “ Hormones and Cancer ”

Ulla Simanainen, T. J. S. Ryan, Desmond Li, Francia Garces Suarez, Yan Gao, Geoff Watson, Yiwei Wang, David J. Handelsman

androgen receptor AR skin cancer DMBA TPA Cox-1 Cox-2 papilloma carcinogenesis tumorigenesis

TLDR Androgen receptor inactivation delays skin cancer onset and reduces incidence in mice, with gender differences in susceptibility.

The study explored the role of androgen receptors (AR) in skin cancer susceptibility in mice, revealing that AR inactivation delayed the onset of skin cancers in both genders when exposed to systemic DMBA treatment, while also reducing cumulative cancer incidence compared to wild-type mice. Male mice were more susceptible to carcinogen-induced skin cancer than females, indicating gender differences in susceptibility. However, in a two-stage carcinogenesis model with local DMBA/TPA treatment, AR inactivation increased papilloma numbers, suggesting different tumorigenesis mechanisms between systemic and local treatments. AR inactivation also altered skin structure and Cox-1 and Cox-2 expression, indicating a molecular mechanism for AR's effect on skin cancer susceptibility, with gender differences persisting even in AR knockout mice.

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