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

Authors
Journal
Molecular and Cellular Endocrinology
0303-7207
Publisher
Elsevier
Publication Date
Volume
87
Identifiers
DOI: 10.1016/0303-7207(92)90229-y
Keywords
  • Insulin-Like Growth Factor-I-Induced Growth
  • Inhibition By 2
  • 3
  • 7
  • 8-Tetrachlorodibenzo-P-Dioxin
  • Mcf-7 Cell
Disciplines
  • Biology
  • Medicine

Abstract

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 K D 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.

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