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- Title
Modulation of basal and squamous cell carcinoma by endogenous estrogen in mouse models of skin cancer.
- Authors
Mancuso, M.; Gallo, D.; Leonardi, S.; Pierdomenico, M.; Pasquali, E.; De Stefano, I.; Rebessi, S.; Tanori, M.; Scambia, G.; Di Majo, V.; Covelli, V.; Pazzaglia, S.; Saran, A.
- Abstract
Patched1 heterozygous mice (Ptch1+/−) are useful for basal cell carcinoma (BCC) studies, being remarkably susceptible to BCC induction by ultraviolet or ionizing radiation. Analogously, skin carcinogenesis-susceptible (Car-S) mice are elective for studies of papilloma and squamous cell carcinoma (SCC) induction. We previously reported a striking effect of gender on BCC induction in Ptch1+/− mice, with total resistance of females; likewise, Car-S females show increased skin tumor resistance relative to males. Here, we investigated the protective role of endogenous estrogen in skin keratinocyte tumorigenesis. Control (CN) and ovariectomized Ptch1+/− or Car-S females were irradiated for BCC induction or topically treated with chemical carcinogens for SCC induction. Susceptibility to BCC or SCC was dramatically increased in ovariectomized Ptch1+/− and Car-S females and restored to levels observed in males. Remarkably, progression of initially benign papillomas to malignant SCC occurred only in ovariectomized Car-S females. We explored the mechanisms underlying tumor progression and report overexpression of estrogen receptor (ER)-α, downregulation of ERβ and upregulation of cyclin D1 in papillomas from ovariectomized Car-S relative to papillomas from CN females. Thus, an imbalanced ERα/ERβ expression may be associated with estrogen-mediated modulation of non-melanoma skin carcinogenesis, with a key role played by cyclin D1. Our findings underscore a highly protective role of endogenous estrogen against skin tumorigenesis by diverse agents in two independent mouse models of skin cancer.
- Subjects
BASAL cell carcinoma; CARCINOGENESIS; ESTROGEN; PAPILLOMA; CARCINOGENS
- Publication
Carcinogenesis, 2009, Vol 30, Issue 2, p340
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgn243