Bombesin activates MAP kinase in non-small cell lung cancer cells

The effects of bombesin (BB) on mitogen activated protein (MAP) kinase were investigated using non-small cell lung cancer (NSCLC) cells. By Western bl ot, both 42 and 44 kDalton forms of MAP kinase were present in NCI-H1299 an d NCI-H838 cells. Addition of BE to NCI-H1299 cells resulted in phosphoryla tion of the MAP kinase substrate myelin basic protein (MBP). Phosphorylatio n of MBP was maximal 6 min after the addition of 10 nM BE to NCI-H1299 cell s. Addition of gastrin releasing peptide (GRP) or GRP(14-27) but not GRP(1- 16) to NCI-H1299 cells caused MBP phosphorylation. The effects of BE were i nhibited by BW2258U89, a BE receptor antagonist, and PD98059, a MAP kinase kinase inhibitor. Also, PD98059 inhibited the clonal growth of NCI-H1299 ce lls. These data suggest that MAP kinase may be an important regulatory enzy me in NSCLC. (C) 1999 by Elsevier Science Inc.