Decreased focal adhesion kinase suppresses papilloma formation during experimental mouse skin carcinogenesis.

Abstract	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.
Authors	G W McLean, K Brown, M I Arbuckle, A W Wyke, T Pikkarainen, E Ruoslahti, M C Frame
Journal	Cancer research (Cancer Res) Vol. 61 Issue 23 Pg. 8385-9 (Dec 01 2001) ISSN: 0008-5472 [Print] United States
PMID	11731413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Carcinogens 9,10-Dimethyl-1,2-benzanthracene Protein-Tyrosine Kinases Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Ptk2 protein, mouse ras Proteins
Topics	9,10-Dimethyl-1,2-benzanthracene Animals Carcinogens Female Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Gene Dosage Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Keratinocytes (drug effects, enzymology, physiology) Male Mice Mice, Inbred C57BL Papilloma (chemically induced, enzymology, genetics) Protein-Tyrosine Kinases (biosynthesis, genetics) Signal Transduction Skin Neoplasms (chemically induced, enzymology, genetics) ras Proteins (physiology)

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