Activation of extracellular signal-regulated kinase mediates bombesin-induced mitogenic responses in prostate cancer cells.
Bombesin and its mammalian homologue gastrin-releasing peptide have been shown to be highly expressed and secreted by neuroendocrine cells in prostate cancer, and are thought to be related to the carcinogenesis and progression of this disease. We found, in this study, bombesin specifically induced mitogen-activated protein (MAP) kinase activation as shown by increased extracellular regulated kinase (ERK) phosphorylation and epidermal growth factor (EGF) receptor transactivation in prostate cancer cells, which express functional gastrin-releasing peptide receptor. The transactivation of EGF receptor was required for bombesin-induced ERK phosphorylation. Furthermore, non-receptor tyrosine kinase Src and cellular Ca2+ were shown to be involved in bombesin-induced EGF receptor transactivation and ERK phosphorylation. Inhibition of either EGF receptor transactivation or ERK activation blocked bombesin-induced DNA synthesis in these cells. Taken together, these data suggest bombesin may act as a mitogen in prostate cancer by activating MAP kinase pathway via EGFR transactivation.
Xiao
Dongmei
D
Section of Gastroenterology, Department of Medicine, Boston University School of Medicine, 650 Albany Street, EBRC, Room 515, Boston, MA 02118, USA.
Qu
Xiangping
X
Weber
H Christian
HC
D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002455:Cell Division; D045744:Cell Line, Tumor; D004247:DNA / Q000096:biosynthesis; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000494:pharmacology
D008934:Mitogens; D015534:Trans-Activators; D004247:DNA; D066246:ErbB Receptors; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases; D020827:rap1 GTP-Binding Proteins; D018631:ras Proteins; D001839:Bombesin; D002118:Calcium