Antagonists of growth hormone-releasing hormone arrest the growth of MDA-MB-468 estrogen-independent human breast cancers in nude mice

Z. Kahán, József L. Varga, Andrew V. Schally, Z. Rékási, Patricia Armatis, Ioulia Chatzistamou, T. Czömpöly, Gábor Halmos

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Since antagonists of growth hormone-releasing hormone (GH-RH) inhibit proliferation of various tumors, in this study we investigated the effects of GH-RH antagonists MZ-5-156 or JV-1-36 on growth of estrogen-independent MDA-MB-468 human breast cancers xenografted into nude mice. Both GH-RH antagonists administered at a dose of 20 μg/day induced regression of some and growth-arrest of other tumors, while control tumors continued to grow. After 5 weeks of therapy with MZ-5-156 or JV-1-36, final volume and weight of MDA-MB-468 tumors were significantly decreased (all p values <0.001) and serum IGF-I levels as well as tumor IGF-I mRNA expression were reduced as compared with controls. High affinity binding sites for IGF-I were detected by the ligand binding method. Gene expression of human IGF-I receptors, as measured by the RT-PCR, was not significantly different in control and treated MDA-MB-468 tumors. In cell culture, IGF-I did not stimulate, GH-RH slightly stimulated, while MZ-5-156 and JV-1-36 inhibited proliferation of MDA-MB-468 cells known to possess defective insulin and IGF-I receptor signaling. The expression of mRNA for human GH-RH was found in five of 8 tumors treated with GH-RH antagonists, and in one of the five control tumors. These results suggest that GH-RH antagonists inhibit MDA-MB-468 breast cancers possibly through mechanisms involving interference with locally produced GH-RH.

Original languageEnglish
Pages (from-to)71-79
Number of pages9
JournalBreast Cancer Research and Treatment
Volume60
Issue number1
DOIs
Publication statusPublished - 2000

Fingerprint

Growth Hormone-Releasing Hormone
Nude Mice
Estrogens
Breast Neoplasms
Hormone Antagonists
Growth
Insulin-Like Growth Factor I
Neoplasms
IGF Type 1 Receptor
Messenger RNA
Human Growth Hormone
Cell Culture Techniques
Binding Sites
Insulin
Ligands
Gene Expression
Weights and Measures
Polymerase Chain Reaction

Keywords

  • Breast cancer
  • GH-RH
  • Growth hormone-releasing hormone (GH-RH) antagonists
  • IGF-I
  • IGF-I receptor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Antagonists of growth hormone-releasing hormone arrest the growth of MDA-MB-468 estrogen-independent human breast cancers in nude mice. / Kahán, Z.; Varga, József L.; Schally, Andrew V.; Rékási, Z.; Armatis, Patricia; Chatzistamou, Ioulia; Czömpöly, T.; Halmos, Gábor.

In: Breast Cancer Research and Treatment, Vol. 60, No. 1, 2000, p. 71-79.

Research output: Contribution to journalArticle

Kahán, Z. ; Varga, József L. ; Schally, Andrew V. ; Rékási, Z. ; Armatis, Patricia ; Chatzistamou, Ioulia ; Czömpöly, T. ; Halmos, Gábor. / Antagonists of growth hormone-releasing hormone arrest the growth of MDA-MB-468 estrogen-independent human breast cancers in nude mice. In: Breast Cancer Research and Treatment. 2000 ; Vol. 60, No. 1. pp. 71-79.
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