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

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

Research output: Contribution to journalArticle

61 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4752-4757
Number of pages6
JournalCancer Research
Volume58
Issue number20
StatePublished - Oct 15 1998

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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