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

H. J. Kim, B. M. Evers, Y. Guo, N. A. Banker, Mark Hellmich, Courtney Townsend

Research output: Contribution to journalArticle

18 Citations (Scopus)

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
StatePublished - 1996

Fingerprint

Bombesin
Transcription Factor AP-1
Stomach Neoplasms
Gastrin-Releasing Peptide
Proto-Oncogene Proteins c-jun
Calcium
Gels
Bombesin Receptors
Messenger RNA
Fura-2
Fluorescence Spectrometry
Second Messenger Systems
Growth
Nuclear Proteins
Protein Binding
Northern Blotting
Transcriptional Activation
Proteins
Western Blotting
RNA

ASJC Scopus subject areas

  • Surgery

Cite this

Kim, H. J., Evers, B. M., Guo, Y., Banker, N. A., Hellmich, M., & Townsend, C. (1996). Bombesin-mediated AP-1 activation in a human gastric cancer (SIIA). Surgery, 120(2), 130-137.

Bombesin-mediated AP-1 activation in a human gastric cancer (SIIA). / Kim, H. J.; Evers, B. M.; Guo, Y.; Banker, N. A.; Hellmich, Mark; Townsend, Courtney.

In: Surgery, Vol. 120, No. 2, 1996, p. 130-137.

Research output: Contribution to journalArticle

Kim, HJ, Evers, BM, Guo, Y, Banker, NA, Hellmich, M & Townsend, C 1996, 'Bombesin-mediated AP-1 activation in a human gastric cancer (SIIA)', Surgery, vol. 120, no. 2, pp. 130-137.
Kim, H. J. ; Evers, B. M. ; Guo, Y. ; Banker, N. A. ; Hellmich, Mark ; Townsend, Courtney. / Bombesin-mediated AP-1 activation in a human gastric cancer (SIIA). In: Surgery. 1996 ; Vol. 120, No. 2. pp. 130-137.
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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.",
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