Synergistic effects of bombesin and epidermal growth factor on cancers

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

Research output: Contribution to journalArticle

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
StatePublished - Apr 26 1994

Fingerprint

Bombesin
Epidermal Growth Factor
Phosphorylation
Neoplasms
Hepatocellular Carcinoma
Gastrin-Releasing Peptide
Mitogens
Cricetinae
Growth
9,10-Dimethyl-1,2-benzanthracene
Cheek
Tumor Cell Line
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-bombesin (6-14)
Epithelial Cells

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Synergistic effects of bombesin and epidermal growth factor on cancers. / Liebow, Charles; Crean, David H.; Lee, Ming T.; Kamer, Angela; Mang, Thomas S.; Schally, Andrew V.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 9, 26.04.1994, p. 3804-3808.

Research output: Contribution to journalArticle

Liebow, Charles ; Crean, David H. ; Lee, Ming T. ; Kamer, Angela ; Mang, Thomas S. ; Schally, Andrew V. / Synergistic effects of bombesin and epidermal growth factor on cancers. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 9. pp. 3804-3808.
@article{94b17372d15c4d00b01574a119a9cc9c,
title = "Synergistic effects of bombesin and epidermal growth factor on cancers",
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.",
keywords = "bombesin antagonist RC-3095, dimethylbenzanthracene, gastrin-releasing peptide, hamster buccal cheek pouch, receptor regulation",
author = "Charles Liebow and Crean, {David H.} and Lee, {Ming T.} and Angela Kamer and Mang, {Thomas S.} and Schally, {Andrew V.}",
year = "1994",
month = "4",
day = "26",
language = "English (US)",
volume = "91",
pages = "3804--3808",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "9",

}

TY - JOUR

T1 - Synergistic effects of bombesin and epidermal growth factor on cancers

AU - Liebow, Charles

AU - Crean, David H.

AU - Lee, Ming T.

AU - Kamer, Angela

AU - Mang, Thomas S.

AU - Schally, Andrew V.

PY - 1994/4/26

Y1 - 1994/4/26

N2 - 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.

AB - 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.

KW - bombesin antagonist RC-3095

KW - dimethylbenzanthracene

KW - gastrin-releasing peptide

KW - hamster buccal cheek pouch

KW - receptor regulation

UR - http://www.scopus.com/inward/record.url?scp=0028302982&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028302982&partnerID=8YFLogxK

M3 - Article

C2 - 8170991

AN - SCOPUS:0028302982

VL - 91

SP - 3804

EP - 3808

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 9

ER -