SCCA2-like serpins mediate genetic predisposition to skin tumors.
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.
Gariboldi
Manuela
M
Department of Experimental Oncology, Istituto Nazionale Tumori 20133, Milan, Italy.
Peissel
Bernard
B
Fabbri
Alessandra
A
Saran
Anna
A
Zaffaroni
Daniela
D
Falvella
F Stefania
FS
Spinola
Monica
M
Tanuma
Jun-ichi
J
Pazzaglia
Simonetta
S
Mancuso
Maria Teresa
MT
Maurichi
Andrea
A
Bartoli
Cesare
C
Cataltepe
Sule
S
Silverman
Gary A
GA
Pilotti
Silvana
S
Hayashizaki
Yoshihide
Y
Okazaki
Yasushi
Y
Dragani
Tommaso A
TA
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
D000951:Antigens, Neoplasm; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; D013755:Tetradecanoylphorbol Acetate