Overexpression of a constitutively active form of c-src in skin epidermis increases sensitivity to tumor promotion by 12-O-tetradecanoylphorbol-13-acetate.

Abstract:

: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.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Matsumoto T,Jiang J,Kiguchi K,Carbajal S,Rho O,Gimenez-Conti I,Beltrán L,DiGiovanni J

doi

10.1002/mc.10030

subject

Has Abstract

pub_date

2002-03-01 00:00:00

pages

146-55

issue

3

eissn

0899-1987

issn

1098-2744

pii

10.1002/mc.10030

journal_volume

33

pub_type

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