J. Leyton et al., Bombesin and gastrin releasing peptide increase tyrosine phosphorylation of focal adhesion kinase and paxillin in non-small cell lung cancer cells, CANCER LETT, 162(1), 2001, pp. 87-95
The effects of some oncogenes, growth factors and neuropeptides are mediate
d by tyrosine phosphorylation of focal adhesion kinase (p125(FAK)) and paxi
llin cytoskeletal proteins. In this study the ability of bombesin/gastrin r
eleasing peptide (BB/GRP) to stimulate tyrosine phosphorylation of p125(FAK
) and paxillin in non-small cell lung cancer (NSCLC) H1299 cells was invest
igated. BB, 100 nM caused increased p125(FAK) and paxillin tyrosine phospho
rylation maximally after 1 min. The effect of BB on p125(FAK) and paxillin
tyrosine phosphorylation was concentration-dependent being half maximal at
4-8 nM. Also, 100 nM GRP, GRP(14-27) but not GRP(1-16) increased p125(FAK)
and paxillin tyrosine phosphorylation indicating that the C-terminal of GRP
is essential. BW2258U89, a GRP receptor antagonist, caused a dose-dependen
t inhibition of BB-stimulated p125(FAK) and paxillin tyrosine phosphorylati
on with an IC50 value of 3 muM. Cytochalasin D (0.3 muM), which inhibits ac
tin polymerization, reduced the ability of BB to stimulate tyrosine phospho
rylation of p125FAK and paxillin. Genistein (50 muM) and H-7 (50 muM), whic
h are kinase inhibitors, reduced the tyrosine phosphorylation of p125(FAK)
and paxillin stimulated by BB. Also, treatment of NCI- H1299 cells with FAK
antisense resulted in decreased FAK tyrosine kinase activity and prolifera
tion. These results suggest that p125(FAK) is,important enzyme for NSCLC pr
oliferation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.