Characterization of receptors for growth hormone-releasing hormone in human osteosarcomas and Ewing's sarcomas

Gabor Halmos, Andrew V Schally, Andrea L F Bernardino, Jozsef L. Varga

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Antagonists of growth hormone-releasing hormone (GH-RH) inhibit growth of various human cancers including osteosarcomas and Ewing's sarcomas, xenografted into nude mice or cultured in vitro. The antiproliferative effect of GH-RH antagonists could be mediated, in part, through the splice variants (SVs) of receptors for GH-RH which have been found in several human cancers and cancer cell lines. In this study we investigated the expression of SVs of GH-RH receptors and the binding characteristics of these receptor isoforms in MNNG/HOS human osteosarcoma and SK-ES-1 human Ewing's sarcoma grown in nude mice. RT-PCR revealed the presence of mRNA for SVs of GH-RH receptors in both human malignant bone cancer models. Using ligand competition assays with 125I-labeled GH-RH antagonist JV-1-42, we demonstrated in MNNG/HOS and SK-ES-1 tumors the presence of specific high affinity binding sites for GH-RH (Kd=5.83 nM and Kd=2.76 nM) with a maximal binding capacity (Bmax) of 552.1 fmol/mg protein and 371.9 fmol/mg protein, respectively. We also investigated the effect of GH-RH antagonist JV-1-38, administered s.c. at a dose of 20 μg twice daily for 4 weeks on the gene expression, affinity and concentration of receptors for GH-RH in MNNG/HOS human osteosarcomas xenografted into nude mice. Treatment with JV-1-38 did not affect the expression and binding characteristics of GH-RH receptors. High affinity binding of JV-1-38 to GH-RH receptors on MNNG/HOS tumors was characterized by an IC50 value of 1.04 nM. The presence of GH-RH receptors in human bone tumors provides a rationale for new approaches to the therapy of this malignancy based on GH-RH antagonists.

Original languageEnglish
Pages (from-to)463-469
Number of pages7
JournalInternational Journal of Oncology
Volume29
Issue number2
StatePublished - Aug 1 2006
Externally publishedYes

Fingerprint

Ewing's Sarcoma
Growth Hormone-Releasing Hormone
Osteosarcoma
Hormone Antagonists
Methylnitronitrosoguanidine
Neoplasms
Nude Mice
Bone Neoplasms
somatotropin releasing hormone receptor
Inhibitory Concentration 50
Protein Isoforms
Proteins
Binding Sites
Ligands
Gene Expression
Bone and Bones
Cell Line
Polymerase Chain Reaction
Messenger RNA
Growth

Keywords

  • GH-RH antagonists
  • GH-RH receptors
  • Human malignant bone tumors
  • Splice variant

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Characterization of receptors for growth hormone-releasing hormone in human osteosarcomas and Ewing's sarcomas. / Halmos, Gabor; Schally, Andrew V; Bernardino, Andrea L F; Varga, Jozsef L.

In: International Journal of Oncology, Vol. 29, No. 2, 01.08.2006, p. 463-469.

Research output: Contribution to journalArticle

@article{9719593d457d4a6591067fdd40d2e061,
title = "Characterization of receptors for growth hormone-releasing hormone in human osteosarcomas and Ewing's sarcomas",
abstract = "Antagonists of growth hormone-releasing hormone (GH-RH) inhibit growth of various human cancers including osteosarcomas and Ewing's sarcomas, xenografted into nude mice or cultured in vitro. The antiproliferative effect of GH-RH antagonists could be mediated, in part, through the splice variants (SVs) of receptors for GH-RH which have been found in several human cancers and cancer cell lines. In this study we investigated the expression of SVs of GH-RH receptors and the binding characteristics of these receptor isoforms in MNNG/HOS human osteosarcoma and SK-ES-1 human Ewing's sarcoma grown in nude mice. RT-PCR revealed the presence of mRNA for SVs of GH-RH receptors in both human malignant bone cancer models. Using ligand competition assays with 125I-labeled GH-RH antagonist JV-1-42, we demonstrated in MNNG/HOS and SK-ES-1 tumors the presence of specific high affinity binding sites for GH-RH (Kd=5.83 nM and Kd=2.76 nM) with a maximal binding capacity (Bmax) of 552.1 fmol/mg protein and 371.9 fmol/mg protein, respectively. We also investigated the effect of GH-RH antagonist JV-1-38, administered s.c. at a dose of 20 μg twice daily for 4 weeks on the gene expression, affinity and concentration of receptors for GH-RH in MNNG/HOS human osteosarcomas xenografted into nude mice. Treatment with JV-1-38 did not affect the expression and binding characteristics of GH-RH receptors. High affinity binding of JV-1-38 to GH-RH receptors on MNNG/HOS tumors was characterized by an IC50 value of 1.04 nM. The presence of GH-RH receptors in human bone tumors provides a rationale for new approaches to the therapy of this malignancy based on GH-RH antagonists.",
keywords = "GH-RH antagonists, GH-RH receptors, Human malignant bone tumors, Splice variant",
author = "Gabor Halmos and Schally, {Andrew V} and Bernardino, {Andrea L F} and Varga, {Jozsef L.}",
year = "2006",
month = "8",
day = "1",
language = "English",
volume = "29",
pages = "463--469",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "2",

}

TY - JOUR

T1 - Characterization of receptors for growth hormone-releasing hormone in human osteosarcomas and Ewing's sarcomas

AU - Halmos, Gabor

AU - Schally, Andrew V

AU - Bernardino, Andrea L F

AU - Varga, Jozsef L.

PY - 2006/8/1

Y1 - 2006/8/1

N2 - Antagonists of growth hormone-releasing hormone (GH-RH) inhibit growth of various human cancers including osteosarcomas and Ewing's sarcomas, xenografted into nude mice or cultured in vitro. The antiproliferative effect of GH-RH antagonists could be mediated, in part, through the splice variants (SVs) of receptors for GH-RH which have been found in several human cancers and cancer cell lines. In this study we investigated the expression of SVs of GH-RH receptors and the binding characteristics of these receptor isoforms in MNNG/HOS human osteosarcoma and SK-ES-1 human Ewing's sarcoma grown in nude mice. RT-PCR revealed the presence of mRNA for SVs of GH-RH receptors in both human malignant bone cancer models. Using ligand competition assays with 125I-labeled GH-RH antagonist JV-1-42, we demonstrated in MNNG/HOS and SK-ES-1 tumors the presence of specific high affinity binding sites for GH-RH (Kd=5.83 nM and Kd=2.76 nM) with a maximal binding capacity (Bmax) of 552.1 fmol/mg protein and 371.9 fmol/mg protein, respectively. We also investigated the effect of GH-RH antagonist JV-1-38, administered s.c. at a dose of 20 μg twice daily for 4 weeks on the gene expression, affinity and concentration of receptors for GH-RH in MNNG/HOS human osteosarcomas xenografted into nude mice. Treatment with JV-1-38 did not affect the expression and binding characteristics of GH-RH receptors. High affinity binding of JV-1-38 to GH-RH receptors on MNNG/HOS tumors was characterized by an IC50 value of 1.04 nM. The presence of GH-RH receptors in human bone tumors provides a rationale for new approaches to the therapy of this malignancy based on GH-RH antagonists.

AB - Antagonists of growth hormone-releasing hormone (GH-RH) inhibit growth of various human cancers including osteosarcomas and Ewing's sarcomas, xenografted into nude mice or cultured in vitro. The antiproliferative effect of GH-RH antagonists could be mediated, in part, through the splice variants (SVs) of receptors for GH-RH which have been found in several human cancers and cancer cell lines. In this study we investigated the expression of SVs of GH-RH receptors and the binding characteristics of these receptor isoforms in MNNG/HOS human osteosarcoma and SK-ES-1 human Ewing's sarcoma grown in nude mice. RT-PCR revealed the presence of mRNA for SVs of GH-RH receptors in both human malignant bone cancer models. Using ligand competition assays with 125I-labeled GH-RH antagonist JV-1-42, we demonstrated in MNNG/HOS and SK-ES-1 tumors the presence of specific high affinity binding sites for GH-RH (Kd=5.83 nM and Kd=2.76 nM) with a maximal binding capacity (Bmax) of 552.1 fmol/mg protein and 371.9 fmol/mg protein, respectively. We also investigated the effect of GH-RH antagonist JV-1-38, administered s.c. at a dose of 20 μg twice daily for 4 weeks on the gene expression, affinity and concentration of receptors for GH-RH in MNNG/HOS human osteosarcomas xenografted into nude mice. Treatment with JV-1-38 did not affect the expression and binding characteristics of GH-RH receptors. High affinity binding of JV-1-38 to GH-RH receptors on MNNG/HOS tumors was characterized by an IC50 value of 1.04 nM. The presence of GH-RH receptors in human bone tumors provides a rationale for new approaches to the therapy of this malignancy based on GH-RH antagonists.

KW - GH-RH antagonists

KW - GH-RH receptors

KW - Human malignant bone tumors

KW - Splice variant

UR - http://www.scopus.com/inward/record.url?scp=39049196032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39049196032&partnerID=8YFLogxK

M3 - Article

VL - 29

SP - 463

EP - 469

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 2

ER -