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

Although focal adhesion kinase (FAK) is elevated in epithelial cancers, it is not known whether FAK expression influences tumor development ill vivo. We found that fak +/- heterozygous mice display reduced 7,12-dimethylbenz[a ]anthracene-induced papilloma formation that correlates with reduced FAK pr otein expression in the skin. However, the frequency of malignant conversio n of papillomas into carcinomas is indistinguishable in fak +/- mice and th eir wild-type fak +/+ littermates, most likely because papilloma FAK protei n expression is elevated to wild-type levels. We also found that keratinocy te FAK protein expression is important for cellular responses downstream of ras in vitro (monitored by extracellular signal-regulated kinase activatio n after integrin engagement). Because 7,12-dimethylbenz[a]anthracene induce s an activating mutation of H-ras, this provides one possible explanation f or suppression of papilloma formation when FAK protein is limiting.