A potent bombesin receptor antagonist inhibits bombesin-stimulated growth of mouse colon cancer cells in vitro

absence of autocrine effects.

S. Narayan, E. R. Spindel, N. H. Rubin, Pomila Singh

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Bombesin (BBS) exerts significant effects on the growth of a mouse colon cancer cell line (MC-26) in vitro. The presence of specific binding sites on MC-26 cells for gastrin-releasing peptide (GRP)/BBS-related peptides was recently reported by us. In the present study, we determined that the transcript size of the mRNA species that codes for GRP receptors is 9 kilobase pairs, which is similar to that reported for mouse Swiss 3T3 cells, using the complementary DNA probe for the GRP receptor gene from mouse Swiss 3T3 cells. We next examined the effects of potent GRP receptor antagonists, D-Phe6, bombesin(6-13)-propylamide (D-Phe6,BN(6-13)PA) and Leu13-psi-(CH2NH)Leu14-bombesin (LL-BBS), on BBS-stimulated growth of MC-26 cells in vitro. A possible autocrine role of GRP in the growth of MC-26 cells was also investigated. MC-26 cells were inoculated s.c. into male BALB/c mice, and tumors were harvested 21-28 days postinoculation. Both D-Phe6,BN(6-13)PA and LL-BBS significantly inhibited the binding of 125I-GRP to MC-26 tumor membranes in a dose-dependent manner, with 50% inhibitory concentrations of 4.5 +/- 0.52 nM and 87 +/- 6 nM, respectively. D-Phe6,BN(6-13)PA similarly inhibited the specific binding of 125I-GRP, cross-linked to a approximately 80 kilodalton binding protein on the MC-26 tumor membranes. In order to determine whether the BBS receptor antagonist, D-Phe6,BN(6-13)PA, functioned as an antagonist or an agonist of biological functions, we measured the bioefficacy of D-Phe6,BN(6-13)PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Original languageEnglish (US)
Pages (from-to)111-118
Number of pages8
JournalCell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
Volume3
Issue number2
StatePublished - Feb 1992

Fingerprint

Bombesin Receptors
Bombesin
Colonic Neoplasms
Gastrin-Releasing Peptide
Growth
Swiss 3T3 Cells
Neoplasms
Membranes
DNA Probes
In Vitro Techniques
Inhibitory Concentration 50
Carrier Proteins
Complementary DNA
Binding Sites
Cell Line
Messenger RNA
Peptides

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

@article{06d981a2e477459a958a8459f3ac9c44,
title = "A potent bombesin receptor antagonist inhibits bombesin-stimulated growth of mouse colon cancer cells in vitro: absence of autocrine effects.",
abstract = "Bombesin (BBS) exerts significant effects on the growth of a mouse colon cancer cell line (MC-26) in vitro. The presence of specific binding sites on MC-26 cells for gastrin-releasing peptide (GRP)/BBS-related peptides was recently reported by us. In the present study, we determined that the transcript size of the mRNA species that codes for GRP receptors is 9 kilobase pairs, which is similar to that reported for mouse Swiss 3T3 cells, using the complementary DNA probe for the GRP receptor gene from mouse Swiss 3T3 cells. We next examined the effects of potent GRP receptor antagonists, D-Phe6, bombesin(6-13)-propylamide (D-Phe6,BN(6-13)PA) and Leu13-psi-(CH2NH)Leu14-bombesin (LL-BBS), on BBS-stimulated growth of MC-26 cells in vitro. A possible autocrine role of GRP in the growth of MC-26 cells was also investigated. MC-26 cells were inoculated s.c. into male BALB/c mice, and tumors were harvested 21-28 days postinoculation. Both D-Phe6,BN(6-13)PA and LL-BBS significantly inhibited the binding of 125I-GRP to MC-26 tumor membranes in a dose-dependent manner, with 50{\%} inhibitory concentrations of 4.5 +/- 0.52 nM and 87 +/- 6 nM, respectively. D-Phe6,BN(6-13)PA similarly inhibited the specific binding of 125I-GRP, cross-linked to a approximately 80 kilodalton binding protein on the MC-26 tumor membranes. In order to determine whether the BBS receptor antagonist, D-Phe6,BN(6-13)PA, functioned as an antagonist or an agonist of biological functions, we measured the bioefficacy of D-Phe6,BN(6-13)PA.(ABSTRACT TRUNCATED AT 250 WORDS)",
author = "S. Narayan and Spindel, {E. R.} and Rubin, {N. H.} and Pomila Singh",
year = "1992",
month = "2",
language = "English (US)",
volume = "3",
pages = "111--118",
journal = "Molecular Cancer Research",
issn = "1541-7786",
publisher = "American Association for Cancer Research Inc.",
number = "2",

}

TY - JOUR

T1 - A potent bombesin receptor antagonist inhibits bombesin-stimulated growth of mouse colon cancer cells in vitro

T2 - absence of autocrine effects.

AU - Narayan, S.

AU - Spindel, E. R.

AU - Rubin, N. H.

AU - Singh, Pomila

PY - 1992/2

Y1 - 1992/2

N2 - Bombesin (BBS) exerts significant effects on the growth of a mouse colon cancer cell line (MC-26) in vitro. The presence of specific binding sites on MC-26 cells for gastrin-releasing peptide (GRP)/BBS-related peptides was recently reported by us. In the present study, we determined that the transcript size of the mRNA species that codes for GRP receptors is 9 kilobase pairs, which is similar to that reported for mouse Swiss 3T3 cells, using the complementary DNA probe for the GRP receptor gene from mouse Swiss 3T3 cells. We next examined the effects of potent GRP receptor antagonists, D-Phe6, bombesin(6-13)-propylamide (D-Phe6,BN(6-13)PA) and Leu13-psi-(CH2NH)Leu14-bombesin (LL-BBS), on BBS-stimulated growth of MC-26 cells in vitro. A possible autocrine role of GRP in the growth of MC-26 cells was also investigated. MC-26 cells were inoculated s.c. into male BALB/c mice, and tumors were harvested 21-28 days postinoculation. Both D-Phe6,BN(6-13)PA and LL-BBS significantly inhibited the binding of 125I-GRP to MC-26 tumor membranes in a dose-dependent manner, with 50% inhibitory concentrations of 4.5 +/- 0.52 nM and 87 +/- 6 nM, respectively. D-Phe6,BN(6-13)PA similarly inhibited the specific binding of 125I-GRP, cross-linked to a approximately 80 kilodalton binding protein on the MC-26 tumor membranes. In order to determine whether the BBS receptor antagonist, D-Phe6,BN(6-13)PA, functioned as an antagonist or an agonist of biological functions, we measured the bioefficacy of D-Phe6,BN(6-13)PA.(ABSTRACT TRUNCATED AT 250 WORDS)

AB - Bombesin (BBS) exerts significant effects on the growth of a mouse colon cancer cell line (MC-26) in vitro. The presence of specific binding sites on MC-26 cells for gastrin-releasing peptide (GRP)/BBS-related peptides was recently reported by us. In the present study, we determined that the transcript size of the mRNA species that codes for GRP receptors is 9 kilobase pairs, which is similar to that reported for mouse Swiss 3T3 cells, using the complementary DNA probe for the GRP receptor gene from mouse Swiss 3T3 cells. We next examined the effects of potent GRP receptor antagonists, D-Phe6, bombesin(6-13)-propylamide (D-Phe6,BN(6-13)PA) and Leu13-psi-(CH2NH)Leu14-bombesin (LL-BBS), on BBS-stimulated growth of MC-26 cells in vitro. A possible autocrine role of GRP in the growth of MC-26 cells was also investigated. MC-26 cells were inoculated s.c. into male BALB/c mice, and tumors were harvested 21-28 days postinoculation. Both D-Phe6,BN(6-13)PA and LL-BBS significantly inhibited the binding of 125I-GRP to MC-26 tumor membranes in a dose-dependent manner, with 50% inhibitory concentrations of 4.5 +/- 0.52 nM and 87 +/- 6 nM, respectively. D-Phe6,BN(6-13)PA similarly inhibited the specific binding of 125I-GRP, cross-linked to a approximately 80 kilodalton binding protein on the MC-26 tumor membranes. In order to determine whether the BBS receptor antagonist, D-Phe6,BN(6-13)PA, functioned as an antagonist or an agonist of biological functions, we measured the bioefficacy of D-Phe6,BN(6-13)PA.(ABSTRACT TRUNCATED AT 250 WORDS)

UR - http://www.scopus.com/inward/record.url?scp=0026812455&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026812455&partnerID=8YFLogxK

M3 - Article

VL - 3

SP - 111

EP - 118

JO - Molecular Cancer Research

JF - Molecular Cancer Research

SN - 1541-7786

IS - 2

ER -