FUNCTIONAL EXPRESSION OF BOMBESIN RECEPTOR IN MOST ADULT AND PEDIATRIC HUMAN GLIOBLASTOMA CELL-LINES - ROLE IN MITOGENESIS AND IN STIMULATING THE MITOGEN-ACTIVATED PROTEIN-KINASE PATHWAY

Functional bombesin receptors were identified in most human glioblasto ma cell lines examined (similar to 85% of lines). Bombesin stimulated the release of intracellular Ca2+ in human adult (U-373MG, D-247MG, U- 11XMG, U-251MG, D-245MG, U-105MG, D-54MG, A-172MG, and D-270MG lines) and pediatric (SJ-S6 and SJ-G2 lines) glioblastoma cell lines. Stimula tion of the glioblastoma cell line U-373MG with bombesin or gastrin-re leasing peptide (GRP) induced mitogenesis, measured by [H-3]thymidine incorporation into DNA, and stimulated the tyrosine phosphorylation of the mitogen-activated protein (MAP) kinases (Erk1 and Erk2). The stim ulation of the MAP kinase phosphorylation in U-373MG cells was time- a nd peptide concentration-dependent. Both bombesin and GRP showed simil ar potencies in stimulation of intracellular Ca2+ release and activati on of the MAP kinase pathway in U-373MG cells, whereas neuromedin B (N MB) peptide was less potent. Bombesin and GRP induced the release of c ytosolic Ca2+ in a concentration-dependent manner. Because bombesin an d GRP were more potent than NMB peptide in increasing the cytosolic Ca 2+ levels in U-373MG cells, we concluded that the BE, subtype (also kn own as GRP-preferring receptor subtype) of the bombesin receptor is ex pressed in this cell line. The bombesin receptor antagonist ([Leu(13)- psi(CH2NH)Leu(14)]bombesin) blocked bombesin induced Ca2+ release and attenuated MAP kinase activation in U-373MG cells demonstrating that b ombesin is acting through a receptor-dependent mechanism. This study i ndicates that functional bombesin receptors are widely expressed in hu man glioblastoma cell lines. (C) 1997 Elsevier Science Ireland Ltd.