Transforming growth factor β signaling through Smad1 in human breast cancer cells

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Xiaojie Liu
  • Jianbo Yue
  • Randall S. Frey
  • Qichao Zhu
  • Kathleen M. Mulder

Detail(s)

Original languageEnglish
Pages (from-to)4752-4757
Journal / PublicationCancer Research
Volume58
Issue number20
Publication statusPublished - 15 Oct 1998
Externally publishedYes

Abstract

Previous results have suggested that Smad1 transduces signals in response to bone morphogenetic proteins (BMPs), but not in response to transforming growth factor β (TGF-β). Here we investigated the ability of TGF-β to regulate Smad1 phosphorylation, hetero-oligomerization with Smad4, translocation to the nucleus, and transcriptional activation of 3TP- luciferase reporter activity in TGF-β- and BMP-responsive Hs578T human breast cancer cells. We demonstrate that Smad1 was rapidly phosphorylated in vivo in response to both TGF-β3 and BMP2 as determined using an antibody against the epitope-tagged Smad1 being expressed. In addition, both TGF-β3 and BMP2 increased Smad1-Smad4 hetero-oligomerization in Hs578T cells. Visualization of Smad1 nuclear translocation with the aid of green fluorescent protein (GFP) in live cells demonstrated nuclear accumulation of GFP-Smad1 fluorescence in response to either TGF-β or BMP2 stimulation. After ligand stimulation, approximately 60-70% of transfected cells displayed prominent nuclear fluorescence. Expression of Smad1 in Hs578T cells increased the activity of the TGF-β-responsive reporter 3TP-Lux. Moreover, TGF-β treatment further potentiated the effect of Smad1 on 3TP-luciferase activity. Collectively, our results demonstrate that TGF-β as well as BMP can signal through Smad1.

Citation Format(s)

Transforming growth factor β signaling through Smad1 in human breast cancer cells. / Liu, Xiaojie; Yue, Jianbo; Frey, Randall S.; Zhu, Qichao; Mulder, Kathleen M.

In: Cancer Research, Vol. 58, No. 20, 15.10.1998, p. 4752-4757.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review