Luteinizing hormone-releasing hormone antagonists interfere with autocrine and paracrine growth stimulation of MCF-7 mammary cancer cells by insulin-like growth factors

Eli Hershkovitz, Miriam Marbach, Emili Bosin, Joseph Levy, Charles T. Roberts, Derek Leroith, Andrew V. Schally, Yoav Sharoni

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Several studies have supported the idea that LH-releasing hormone (LHRH) antagonists have a direct effect on mammary tumor cells. In this study, we have evaluated the potential role of the insulin-like growth factors (IGFs) on the growth of MCF-7 mammary tumor cells and the effect of LHRH analogs on IGF action. The mitogenic effects of IGF-I, IGF-II, and insulin were compared. IGF-I was found to be 3 times more potent than IGF-II and 30 times more potent than insulin, suggesting that the effects of these growth factors are mediated by the IGF-I receptor. IGFs released by MCF-7 cells were measured by specific RIA after acid extraction and chromatography, so as to avoid the interference of IGF-binding proteins. MCF-7 cells secreted IGF-II, but not IGF-I. Estradiol (10-9 mol/L) stimulated IGF-II release; this release preceded the effect of estradiol on cell growth. The LHRH antagonist [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,D-Cit 6,D-Ala10]LHRH (SB-75, CETRORELIX) inhbited basal, estrogen-induced, and IGF-induced growth. Moreover, this antagonist almost completely inhibited IGF-II release from MCF-7 cells. This effect preceeded the inhibition of tumor cell growth. We conclude that a LHRH antagonist can inhibit the growth of breast tumors by interfering with the automne action of IGF-II and by directly inhibiting the growth stimulatory effect of IGFs.

Original languageEnglish (US)
Pages (from-to)963-968
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume77
Issue number4
DOIs
StatePublished - Oct 1993
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this