Tamoxifen and estrogen effects on TGF-beta formation: role of thrombospondin-1, alphavbeta3, and integrin-associated protein

Biochem Biophys Res Commun. 2001 Jun 1;284(1):11-4. doi: 10.1006/bbrc.2001.4922.

Abstract

We have found that the enhanced activation of latent TGF-beta 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-beta 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 alphavbeta3 and integrin-associated protein (IAP) occurs under these conditions, and antibodies to TSP-1 or to these receptors inhibit increased TGF-beta formation. Therefore, increased cell surface associated TSP-1 enhances latent TGF-beta activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Antibodies, Blocking / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / metabolism
  • Blotting, Northern
  • Breast Neoplasms / metabolism*
  • CD36 Antigens / metabolism
  • CD47 Antigen
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / metabolism
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Estrogen Antagonists / pharmacology
  • Estrogens / pharmacology*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Latent TGF-beta Binding Proteins
  • RNA, Messenger / metabolism
  • Receptors, Vitronectin / antagonists & inhibitors
  • Receptors, Vitronectin / metabolism
  • Tamoxifen / pharmacology*
  • Thrombospondin 1 / antagonists & inhibitors
  • Thrombospondin 1 / metabolism
  • Transforming Growth Factor beta / biosynthesis*
  • Tumor Cells, Cultured

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antigens, CD
  • CD36 Antigens
  • CD47 Antigen
  • CD47 protein, human
  • Carrier Proteins
  • Culture Media, Conditioned
  • Estrogen Antagonists
  • Estrogens
  • Intracellular Signaling Peptides and Proteins
  • Latent TGF-beta Binding Proteins
  • RNA, Messenger
  • Receptors, Vitronectin
  • Thrombospondin 1
  • Transforming Growth Factor beta
  • Tamoxifen