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

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

Research output: Contribution to journalArticle

60 Citations (Scopus)

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

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Transforming Growth Factors
Breast Neoplasms
Bone Morphogenetic Proteins
Green Fluorescent Proteins
Luciferases
Fluorescence
Transcriptional Activation
Epitopes
Phosphorylation
Ligands
Antibodies

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Liu, Xiaojie ; Yue, Jianbo ; Frey, Randall S. ; Zhu, Qichao ; Mulder, Kathleen. / Transforming growth factor β signaling through Smad1 in human breast cancer cells. In: Cancer Research. 1998 ; Vol. 58, No. 20. pp. 4752-4757.
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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.",
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Liu, X, Yue, J, Frey, RS, Zhu, Q & Mulder, K 1998, 'Transforming growth factor β signaling through Smad1 in human breast cancer cells', Cancer Research, vol. 58, no. 20, pp. 4752-4757.

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

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

Research output: Contribution to journalArticle

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T1 - Transforming growth factor β signaling through Smad1 in human breast cancer cells

AU - Liu, Xiaojie

AU - Yue, Jianbo

AU - Frey, Randall S.

AU - Zhu, Qichao

AU - Mulder, Kathleen

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