Bombesin-mediated AP-1 activation in a human gastric cancer (SIIA)

H. J. Kim, B. M. Evers, Y. Guo, N. A. Banker, M. R. Hellmich, Jr Townsend

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Background. Bombesin, a gut tetradecapeptide homologous to the mammalian gastrin-releasing peptide (GRP), stimulates the growth of the human gastric cancer line SIIA through specific GRP receptors (GRP-Rs); the cellular mechanisms are not known. The purpose of our study was to (1) confirm functional GRP-R in SIIA and (2) determine whether bombesin alters the expression and binding activity of the AP-1 transcription factors, c-jun and jun-B. Methods. SIIA cells were treated with bombesin, and intracellular calcium mobilization was measured by means of fura-2 spectrofluorometry. To assess changes in c-jun and jun-B, RNA and protein were extracted for Northern and Western blots, respectively; nuclear protein was extracted for gel mobility shifts to determine AP-1 binding activity. Results. SIIA cells mobilized intracellular calcium in response to bombesin, exhibiting a functional cell-surface GRP-R. Bombesin treatment increased expression op both c-jun and jun-B mRNA by 0.5 hours, with maximal expression at 1 hour; concomitant increases in steady-state levels of c-Jun and JunB protein were identified. Moreover, bombesin increased binding of the AP-1 proteins as shown by gel shifts. Conclusions. The SIIA human gastric cancer possesses functional GRP-R coupled to the calcium second messenger pathway. Further, bombesin stimulates expression of c-jun and jun-B mRNA and protein and increases binding activity of AP-1 proteins. Delineating the cellular pathways involved in bombesin-mediated gene activation will provide important insights into the mechanisms responsible for normal and neoplastic gut growth.

Original languageEnglish (US)
Pages (from-to)130-137
Number of pages8
JournalSurgery
Volume120
Issue number2
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Surgery

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