Modulation of basal and squamous cell carcinoma by endogenous estrogen in mouse models of skin cancer
| Autor: | S. Rebessi, Vincenzo Covelli, Mirella Tanori, Giovanni Scambia, Anna Saran, Mariateresa Mancuso, Maria Pierdomenico, L. De Stefano, Simona Leonardi, Emanuela Pasquali, Simonetta Pazzaglia, Daniela Gallo, V. Di Majo |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Patched Receptors Cancer Research medicine.medical_specialty Neoplasms Radiation-Induced Skin Neoplasms Ultraviolet Rays medicine.drug_class Ovariectomy Estrogen receptor Receptors Cell Surface Biology medicine.disease_cause Mice Cyclin D1 Internal medicine medicine Animals Estrogen Receptor beta Basal cell carcinoma neoplasms Papilloma integumentary system Estrogen Receptor alpha Estrogens General Medicine medicine.disease Patched-1 Receptor Disease Models Animal Cell Transformation Neoplastic Endocrinology medicine.anatomical_structure Carcinoma Basal Cell Estrogen Tumor progression Carcinoma Squamous Cell Female Skin cancer Carcinogenesis Keratinocyte |
| Zdroj: | Carcinogenesis. 30:340-347 |
| ISSN: | 1460-2180 0143-3334 |
| Popis: | 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)-alpha, downregulation of ERbeta and upregulation of cyclin D1 in papillomas from ovariectomized Car-S relative to papillomas from CN females. Thus, an imbalanced ERalpha/ERbeta 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. |
| Databáze: | OpenAIRE |
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