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Abstract
Bombesin (BN) and its mammalian homologue gastrin-releasing peptide (GRP) have been
shown to play an important role in human cancer as autocrine and paracrine growth
factors. Prostatic neuroendocrine cells are thought to secrete these regulatory peptides
and they may therefore interact with their specific, aberrantly expressed GRP receptor
(GRP-R) in prostate cancer. In this study, we investigated the effect of BN on immediate
early gene expression in two androgen-independent prostate cancer cell lines DU-145
and PC-3 with functional GRP receptor. We found that BN induced c-fos mRNA expression
in both cell lines in a time-dependent manner. In contrast, c-jun mRNA was only modestly
induced in DU-145 cells but not at all in PC-3 cells. On the protein level, we detected
BN-induced stimulation of the c-fos gene product but not of c-jun protein. Sustained
increase of the c-myc gene product was detectable in PC-3 but not in DU-145 cells.
Concurrently, we demonstrated BN-dependent activation of the transcription factor
Elk-1 and significant increase of cell proliferation in both prostate cancer cell
lines. Taken together, these data suggest that BN acts as a mitogen in prostate cancer
and this might be associated with the activation of the transcription factor Elk-1
and the immediate early gene c-fos.