Expression of transforming growth factor β (TGFβ) type III receptor restores autocrine TGFβ1 activity in human breast cancer MCF-7 cells

Changguo Chen, Xiao Fan Wang, Lu Zhe Sun

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

While transforming growth factor β (TGFβ) type III receptor (RIII) is known to increase TGFβ1 binding to its type II receptor (RII), the significance of this phenomenon is not known. We used human breast cancer MCF-7 cells to study the role of RIII in regulating autocrine TGFβ1 activity because they express very little RIII and no detectable autocrine TGFβ activity. A tetracycline-repressible RIII expression vector was stably transfected into this cell line. Expression of RIII increased TGFβ1 binding to TGFβ type I receptor (RI) as well as RII. Treatment with tetracycline suppressed RIII expression and abolished TGFβ1 binding to RI and RII. Growth of RIII-transfected cells was reduced by 40% when plated at low density on plastic. This reduction was reversed by tetracycline treatment and was partially reversed by treatment with a TGFβ1 neutralizing antibody. The activity of a TGFβ1-responsive promoter construct when transiently transfected was more than 3-fold higher in the RIII-transfected cells than in the control cells. Treating the cells with tetracycline or the TGFβ1 neutralizing antibody also significantly attenuated the increased promoter activity. These results suggest that expression of RIII restored autocrine TGFβ1 activity in MCF-7 cells. The RIII-transfected cells were also much less clonogenic in soft agarose than the control cells indicating a reversion of progression. Thus, RIII may be essential for an optimal level of the autocrine TGFβ activity in some cells, especially in the transformed cells with reduced RII expression.

Original languageEnglish (US)
Pages (from-to)12862-12867
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number19
DOIs
StatePublished - May 9 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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