Tamoxifen and estrogen effects on TGF-β formation: Role of thrombospondin-1, αvβ3, and integrin-associated protein

Academic Article

Abstract

  • We have found that the enhanced activation of latent TGF-β by human breast carcinoma cell lines either treated with tamoxifen or deprived of estrogen is dependent upon thrombospondin-1 (TSP-1) since activation was blocked by anti-TSP-1 antibodies or by a TSP antagonist peptide. However, TGF-β formation upon tamoxifen exposure to estrogen withdrawal is associated with decreased levels of soluble TSP-1. A concomitant increase in the expression of the TSP-1 receptors αvβ3 and integrin-associated protein (IAP) occurs under these conditions, and antibodies to TSP-1 or to these receptors inhibit increased TGF-β formation. Therefore, increased cell surface associated TSP-1 enhances latent TGF-β activation. © 2001 Academic Press.
  • Digital Object Identifier (doi)

    Author List

  • Harpel JG; Schultz-Cherry S; Murphy-Ullrich JE; Rifkin DB
  • Start Page

  • 11
  • End Page

  • 14
  • Volume

  • 284
  • Issue

  • 1