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

G W McLean, K Brown, M I Arbuckle, A W Wyke, T Pikkarainen, E Ruoslahti, M C Frame

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)8385-9
Number of pages5
JournalCancer Research
Issue number23
Publication statusPublished - 1 Dec 2001

Keywords / Materials (for Non-textual outputs)

  • 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
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Papilloma
  • Protein-Tyrosine Kinases
  • Signal Transduction
  • Skin Neoplasms
  • ras Proteins


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