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Modulation of basal and squamous cell carcinoma by endogenous estrogen in mouse models of skin cancer

TitleModulation of basal and squamous cell carcinoma by endogenous estrogen in mouse models of skin cancer
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2009
AuthorsMancuso, Mariateresa, Gallo D., Leonardi Simona, Pierdomenico Maria, Pasquali Emanuela, De Stefano L., Rebessi S., Tanori Mirella, Scambia G., Di Majo V., Covelli V., Pazzaglia Simonetta, and Saran Anna
JournalCarcinogenesis
Volume30
Pagination340-347
ISSN01433334
Keywordsanimal, animal experiment, animal model, animal tissue, Animals, article, Basal Cell, basal cell carcinoma, cancer growth, carcinogen, Carcinoma, Cell Surface, Cell Transformation, controlled study, cyclin D1, Disease Models, down regulation, estrogen, estrogen receptor alpha, estrogen receptor beta, Estrogens, Female, immunohistochemistry, irradiation, keratinocyte, male, Mice, mouse, Neoplasms, Neoplastic, nonhuman, ovariectomy, papilloma, priority journal, Radiation-Induced, Receptors, reverse transcription polymerase chain reaction, RNA, RNA extraction, skin carcinogenesis, skin carcinoma, Skin Neoplasms, Squamous Cell, squamous cell carcinoma, Ultraviolet Rays, upregulation
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. © The Author 2008. Published by Oxford University Press. All rights reserved.

Notes

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-60149098270&doi=10.1093%2fcarcin%2fbgn243&partnerID=40&md5=157550c88211c14aaada8812b74e273f
DOI10.1093/carcin/bgn243
Citation KeyMancuso2009340