Decreased focal adhesion kinase suppresses papilloma formation during experimental mouse skin carcinogenesis
| Autor: | G W, McLean, K, Brown, M I, Arbuckle, A W, Wyke, T, Pikkarainen, E, Ruoslahti, M C, Frame |
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| Rok vydání: | 2001 |
| Předmět: |
Keratinocytes
Male Skin Neoplasms Papilloma 9 10-Dimethyl-1 2-benzanthracene Gene Dosage Protein-Tyrosine Kinases Gene Expression Regulation Enzymologic Gene Expression Regulation Neoplastic Mice Inbred C57BL Mice Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Carcinogens ras Proteins Animals Female Signal Transduction |
| Zdroj: | Cancer research. 61(23) |
| ISSN: | 0008-5472 |
| Popis: | Although focal adhesion kinase (FAK) is elevated in epithelial cancers, it is not known whether FAK expression influences tumor development in vivo. We found that fak +/- heterozygous mice display reduced 7,12-dimethylbenz[a]anthracene-induced papilloma formation that correlates with reduced FAK protein expression in the skin. However, the frequency of malignant conversion of papillomas into carcinomas is indistinguishable in fak +/- mice and their wild-type fak +/+ littermates, most likely because papilloma FAK protein expression is elevated to wild-type levels. We also found that keratinocyte FAK protein expression is important for cellular responses downstream of ras in vitro (monitored by extracellular signal-regulated kinase activation after integrin engagement). Because 7,12-dimethylbenz[a]anthracene induces an activating mutation of H-ras, this provides one possible explanation for suppression of papilloma formation when FAK protein is limiting. |
| Databáze: | OpenAIRE |
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