title: 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.affiliation: Beatson Institute for Cancer Research, Garscube Estate, Bearsden, Glasgow G61 1BD, United Kingdom.
authors.forename: G W
authors.initials: GW
authors.lastname: McLean
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.forename: M I
authors.initials: MI
authors.lastname: Arbuckle
authors.forename: A W
authors.initials: AW
authors.lastname: Wyke
authors.forename: T
authors.initials: T
authors.lastname: Pikkarainen
authors.forename: E
authors.initials: E
authors.lastname: Ruoslahti
authors.forename: M C
authors.initials: MC
authors.lastname: Frame
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D018628:Gene Dosage; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010212:Papilloma / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D018631:ras Proteins / Q000502:physiology
chemical_list: D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D018631:ras Proteins