Synergistic effects of bombesin and epidermal growth factor on cancers

Charles Liebow, David H. Crean, Ming T. Lee, Angela R. Kamer, Thomas S. Mang, Andrew V. Schally

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Bombesin and gastrin-releasing peptide act as autocrine mitogens in various cancers. Bombesin antagonist RC-3095 inhibited growth in some cancers and slowed the progression of premalignant lesions, possibly by down- regulating epidermal growth factor (EGF) receptors. Since the EGF receptor mitogen response involves tyrosine kinase stimulation, we tested the hypotheses that bombesin stimulates, and RC-3095 inhibits, phosphorylation; EGF and bombesin promote the phosphorylation of the same substrates; and EGF and bombesin act synergistically on phosphorylation. Therefore, in vitro assays for phosphorylation were performed in the presence or absence of EGF, bombesin, RC-3095, and combinations in samples derived from tumor, tissue surrounding tumor, cell lines, and normal and transforming tissue derived from the 9,10-dimethyl-1,2-benzanthracene-induced squamous cell lesions of the hamster cheek pouch. Bombesin increased, and RC-3095 decreased, phosphorylation in these samples. In the human hepatoma sample and surrounding tissue, these ligands altered the phosphorylation of the same substrates affected by EGF. EGF and bombesin stimulated phosphorylation synergistically in the hamster samples and the hepatoma. Bombesin-induced phosphorylation was greater in tissue surrounding the hepatoma, whereas RC- 3095 was more effective in inhibiting phosphorylation in the hepatoma itself. This cancer, therefore, could be endogenously stimulated by gastrin-releasing peptide. These observations support the hypothesis that bombesin stimulates growth of tissues and tumors by amplifying the phosphorylation response to EGF. The growth inhibitory response to RC-3095, or other bombesin analogues, of individual tumors may be prognosed by in vitro phosphorylation assays using the samples from the patient's tumor.

Original languageEnglish (US)
Pages (from-to)3804-3808
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number9
DOIs
StatePublished - Apr 26 1994
Externally publishedYes

Keywords

  • bombesin antagonist RC-3095
  • dimethylbenzanthracene
  • gastrin-releasing peptide
  • hamster buccal cheek pouch
  • receptor regulation

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'Synergistic effects of bombesin and epidermal growth factor on cancers'. Together they form a unique fingerprint.

Cite this