title: SCCA2-like serpins mediate genetic predisposition to skin tumors.
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.
authors.affiliation: Department of Experimental Oncology, Istituto Nazionale Tumori 20133, Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Gariboldi
authors.forename: Bernard
authors.initials: B
authors.lastname: Peissel
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabbri
authors.forename: Anna
authors.initials: A
authors.lastname: Saran
authors.forename: Daniela
authors.initials: D
authors.lastname: Zaffaroni
authors.forename: F Stefania
authors.initials: FS
authors.lastname: Falvella
authors.forename: Monica
authors.initials: M
authors.lastname: Spinola
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Tanuma
authors.forename: Simonetta
authors.initials: S
authors.lastname: Pazzaglia
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Mancuso
authors.forename: Andrea
authors.initials: A
authors.lastname: Maurichi
authors.forename: Cesare
authors.initials: C
authors.lastname: Bartoli
authors.forename: Sule
authors.initials: S
authors.lastname: Cataltepe
authors.forename: Gary A
authors.initials: GA
authors.lastname: Silverman
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Tommaso A
authors.initials: TA
authors.lastname: Dragani
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015843:Serpins / Q000096:biosynthesis / Q000235:genetics*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; D013755:Tetradecanoylphorbol Acetate