Inhibition of insulin-like growth factor-I responses in MCF-7 cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds

H. Liu, L. Biegel, T. R. Narasimhan, C. Rowlands, S. Safe

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Insulin-like growth factor-I (IGF-I) stimulated the growth and [3H]thymidine uptake in MCF-7 human breast cancer cells grown in serum- and growth factor-inactivated serum-containing media. Cotreatment of the cells with IGF-I plus 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in a significant decrease in mitogen-induced cell proliferation and [3H]thymidine uptake. Similar effects were observed for cells treated with 2,3,7,8-TCDD and IGF-I plus 17β-estradiol. The relative antimitogenic activities of 2,3,7,8-TCDD and related compounds followed the order 2,3,7,8-TCDD > 2,3,7,8-tetrachlorodi benzofuran (TCDF) > 1,2,7,8-TCDF > 1,3,7,8-TCDD which was similar to their aryl hydrocarbon (Ah) receptor binding affinities. The results showed that 2,3,7,8-TCDD did not alter the IGF-I receptor mRNA levels or the KD values for binding of [125I]IGF-I to the IGF-I receptor in MCF-7 cells. However, 2,3,7,8-TCDD significantly decreased the number of IGF-I-induced IGF-I receptor binding sites and this may play a role in the growth-inhibitory properties of 2,3,7,8-TCDD and related compounds and in the 'cross-talk' between the two endocrine-response pathways.

Original languageEnglish (US)
Pages (from-to)19-28
Number of pages10
JournalMolecular and cellular endocrinology
Volume87
Issue number1-3
DOIs
StatePublished - Sep 1992

Keywords

  • Inhibition by 2,3,7,8-tetrachlorodibenzo-p-dioxin
  • Insulin-like growth factor-I-induced growth
  • MCF-7 cell

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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