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Overexpression of a constitutively active form of c‐src in skin epidermis increases sensitivity to tumor promotion by 12‐ O ‐tetradecanoylphorbol‐13‐acetate
Author(s) -
Matsumoto Takashi,
Jiang Jianghong,
Kiguchi Kaoru,
Carbajal Steve,
Rho Okkyung,
GimenezConti Irma,
Beltrán Linda,
DiGiovanni John
Publication year - 2002
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10030
Subject(s) - tumor promotion , biology , 12 o tetradecanoylphorbol 13 acetate , epidermis (zoology) , proto oncogene tyrosine protein kinase src , carcinogenesis , transgene , genetically modified mouse , hyperplasia , cancer research , phenotype , tetradecanoylphorbol acetate , endocrinology , kinase , microbiology and biotechnology , medicine , protein kinase c , cancer , biochemistry , phorbol ester , gene , genetics , anatomy
Transgenic mice were developed to study the role of c‐src in epithelial tumorigenesis through targeted expression of a constitutively active form of murine c‐src (src 529 ). Src 529 was targeted to the interfollicular epidermis with the human keratin 1 (HK1) promoter. The skin phenotype of these mice was characterized by exaggerated epidermal hyperplasia and hyperkeratosis within the first week after birth. The severity of this phenotype correlated with overall src kinase activity, both of which subsided with age. Treatment of adult HK1.src 529 transgenic mice with the phorbol ester tumor promoter 12‐ O ‐tetradecanoylphorbol‐13‐acetate resulted in an increase in epidermal hyperplasia and labeling index significantly greater than that seen in nontransgenic littermates. In addition, HK1.src 529 transgenic mice developed papillomas earlier and in significantly greater numbers compared with nontransgenic littermates in a standard initiation‐promotion experiment. The data support the hypothesis that activation of c‐src kinase plays a role in skin tumor promotion. © 2002 Wiley‐Liss, Inc.