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[Cancer Research 63, 1871-1875, April 15, 2003]
© 2003 American Association for Cancer Research

Molecular Biology and Genetics

SCCA2-like Serpins Mediate Genetic Predisposition to Skin Tumors1

Manuela Gariboldi2, Bernard Peissel2, Alessandra Fabbri, Anna Saran, Daniela Zaffaroni, F. Stefania Falvella, Monica Spinola, Jun-ichi Tanuma, Simonetta Pazzaglia, Maria Teresa Mancuso, Andrea Maurichi, Cesare Bartoli, Sule Cataltepe, Gary A. Silverman, Silvana Pilotti, Yoshihide Hayashizaki, Yasushi Okazaki and Tommaso A. Dragani3

Departments of Experimental Oncology [M. G., B. P., D. Z., F. S. F., M. S., J-i. T., T. A. D.], Pathology [A. F., S. P.], and Surgical Day Hospital [A. M., C. B.], Istituto Nazionale Tumori 20133, Milan, Italy; Laboratory for Genome Exploration Research Group, RIKEN Genomic Sciences Center, RIKEN Yokohama Institute, Yokohama-city, Kanagawa 230-0045, Japan [M. G., Y. H., Y. O.]; ENEA CR Casaccia 00060, Rome, Italy [A. S., S. P., M. T. M.]; and Division of Newborn Medicine, Department of Pediatrics, Harvard Medical School, Children’s Hospital, Boston, Massachusetts 02115-5737 [S. C., G. A. S.]

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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Copyright © 2003 by the American Association for Cancer Research.