SCCA2-like serpins mediate genetic predisposition to skin tumors |
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Authors: | Gariboldi Manuela Peissel Bernard Fabbri Alessandra Saran Anna Zaffaroni Daniela Falvella F Stefania Spinola Monica Tanuma Jun-ichi Pazzaglia Simonetta Mancuso Maria Teresa Maurichi Andrea Bartoli Cesare Cataltepe Sule Silverman Gary A Pilotti Silvana Hayashizaki Yoshihide Okazaki Yasushi Dragani Tommaso A |
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Affiliation: | Department of Experimental Oncology, Istituto Nazionale Tumori 20133, Milan, Italy. |
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Abstract: | Reasons for early onset skin cancer are poorly understood. Microarray analysis revealed overexpression of the Scca2 gene in the 12-O-tetradecanoylphorbol-13-acetate-treated skin of Car-S mice, or line phenotypically selected for high susceptibility to two-stage skin carcinogenesis, as compared with 12-O-tetradecanoylphorbol-13-acetate-treated skin of Car-R mice, which is resistant. A human skin squamous cell carcinoma cell line (NCI-H520) transfected with mouse Scca2 or a related gene, Scca2-rs1, both expressed in the skin, showed significantly increased tumor growth as compared with controls when injected in nude mice. Immunohistochemical analysis of samples from two independent series of Italian and Korean patients with squamous cell carcinoma of the skin indicated a significant association between SCCA2 protein expression and younger age at tumor onset. These findings provide evidence that SCCA2-like serpins mediate genetic predisposition to skin cancer in a mouse model and in humans. |
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