Inhibition of growth and metastases of MDA-MB-435 human estrogen-independent breast cancers by an antagonist of growth hormone-releasing hormone

Ioulia Chatzistamou, Andrew V Schally, Jozsef L. Varga, Kate Groot, Rebeca Busto, Patricia Armatis, Gabor Halmos

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Antagonists of growth hormone-releasing hormone (GH-RH) inhibit the growth of various cancers by mechanism(s) that include the suppression of the insulin-like growth factors (IGF)-I and/or -II. In this study, nude mice bearing orthotopic implants of MDA-MB-435 human estrogen-independent breast carcinoma received 39 days of therapy with GH-RH antagonist JV-1-36 (20 μg/day). The treatment significantly inhibited tumor growth by 71.1% (p<0.01) and nullified the metastatic potential of MDA-MB-435 cells. Four of eight control mice (50%) developed metastases in the lymph nodes and one (12.5%) in the lung, but none of the animals receiving JV-1-36 showed metastatic spread. GH-RH antagonist JV-1-36 inhibited the growth of MDA-MB-435 cells in vitro, while IGF-I stimulated it. However, mRNA for IGF-I or -II was not detected in MDA-MB-435 cells, indicating that the suppression of autocrine IGFs may not be involved in the antiproliferative mechanism. Using ligand competition assays with 125I-labeled GH-RH antagonist JV-1-42, specific high-affinity binding sites for GH-RH were found on tumor membranes. Reverse transcription-polymerase chain reaction revealed the expression of mRNA for GH-RH receptor splice variant-1 in MDA-MB-435 tumors. Our results suggest that the antitumorigenic action of GH-RH antagonists on MDA-MB-435 breast cancer could be direct and mediated by tumoral GH-RH receptors.

Original languageEnglish
Pages (from-to)761-768
Number of pages8
JournalAnti-Cancer Drugs
Volume12
Issue number9
DOIs
StatePublished - Nov 7 2001
Externally publishedYes

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Keywords

  • Breast cancer therapy
  • Growth hormone-releasing hormone antagonists
  • Growth hormone-releasing hormone receptor
  • Insulin-like growth factors

ASJC Scopus subject areas

  • Pharmacology
  • Cancer Research
  • Oncology

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