|Title||SCCA2-like serpins mediate genetic predisposition to skin tumors|
|Publication Type||Articolo su Rivista peer-reviewed|
|Year of Publication||2003|
|Authors||Gariboldi, M., Peissel B., Fabbri A., Saran Anna, Zaffaroni D., F. Falvella Stefania, Spinola M., Tanuma J.-I., Pazzaglia Simonetta, Mancuso Mariateresa, Maurichi A., Bartoli C., Cataltepe S., Silverman G.A., Pilotti S., Hayashizaki Y., Okazaki Y., and Dragani T.A.|
|Keywords||adult, aged, animal cell, Animals, antigen expression, Antigens, article, Carcinoma, Cell Division, complementary DNA, controlled study, disease association, DNA microarray, gene function, gene overexpression, genetic association, Genetic Predisposition to Disease, genetic susceptibility, genetic transfection, human, human cell, Humans, immunohistochemistry, male, Mice, Middle Aged, mouse, mouse strain, Neoplasm, nonhuman, Nude, nude mouse, Oligonucleotide Array Sequence Analysis, Phenotype, phorbol 13 acetate 12 myristate, priority journal, protein family, protein function, serine proteinase inhibitor, serology, Serpins, skin carcinogenesis, Skin Neoplasms, skin tumor, Squamous Cell, squamous cell carcinoma 2 antigen, Tetradecanoylphorbol Acetate, Transfection, tumor antigen, unclassified drug|
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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