Journal Article

Epidermal hyperplasia and papillomatosis in mice with a keratinocyte-restricted deletion of <i>csk</i>

Kazuhisa Honda, Takehisa Sakaguchi, Keiko Sakai, Christian Schmedt, Angel Ramirez, Jose Luis Jorcano, Alexander Tarakhovsky, Hiroshi Kamisoyama and Takao Sakai

in Carcinogenesis

Volume 28, issue 10, pages 2074-2081
Published in print October 2007 | ISSN: 0143-3334
Published online May 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm112
Epidermal hyperplasia and papillomatosis in mice with a keratinocyte-restricted deletion of csk

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The Src family kinases (SFKs) are believed to play critical roles in malignant transformation, as well as in growth, invasion and dissemination of neoplastic tissue. Inhibition of SFK-mediated signal transduction and activation of downstream targets inhibits tumor progression. To determine whether constitutive activity of SFK per se is sufficient to induce tumorigenesis in vivo, we have generated a mouse model with a keratinocyte-restricted deletion of the SFK-negative regulator csk (Csk-K5 mice). Even though expression levels of SFKs were lower in C-terminal Src kinase (Csk)-null keratinocytes, activity levels were higher than in control keratinocytes. At the age of 3 months, all Csk-K5 mice displayed signs of chronic inflammation in dermis and epidermal hyperplasia. About 19% of Csk-K5 mice (7 out of 36) developed papillomatous lesions. However, these lesions did not show any signs of neoplastic transformation over the next 8 months. Epidermal hyperplasia and hyperkeratosis in Csk-K5 mice were associated with an increased number of stem cells in the interfollicular epidermis, an increased proliferation of basal keratinocytes and a delayed terminal differentiation of the suprabasal keratinocytes. Our results clearly demonstrate that even though SFK-mediated signaling promotes tumor progression, elevated activity of SFKs in vivo alone is not sufficient to induce neoplastic transformation.

Journal Article.  6031 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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