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  • Original Paper
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Autocrine TGFβ supports growth and survival of human breast cancer MDA-MB-231 cells

Oncogene volume 21, pages 7514–7523 (2002)Cite this article

Abstract

Using a cell model system established by ectopic expression of a soluble TGFβ type III receptor (sRIII) containing the whole extracellular domain of the type III receptor in human breast cancer MDA-MB-231 cells, we observed that the expression of sRIII antagonized TGFβ activity and inhibited both anchorage-dependent and anchorage-independent cell growth. Further studies revealed that sRIII expression induced apoptosis both in vitro and in vivo. Treatment with TGFβ neutralizing antibodies or a recombinant human sRIII also induced apoptosis in the MDA-MB-231 parental cells, suggesting that the increased apoptosis after sRIII expression was specifically due to antagonization of autocrine TGFβ signaling. Western blotting showed that sRIII clones had a higher PTEN expression level than the control cells did. Treatment with TGFβ1 decreased PTEN and inhibited apoptosis in sRIII cells to a level similar to that in the control cells. sRIII clones also showed a lower level of phosphorylated-Akt than the control cells, consistent with the inhibitory activity of PTEN on Akt activation. Treatment with LY294002, a specific inhibitor of Akt activator, phosphatidylinositol 3-kinase, also induced apoptosis in a dose dependent manner in the control cells. Our results suggest that autocrine TGFβ signaling is necessary for the growth and survival of MDA-MB-231 cells.

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Acknowledgements

This work was supported by National Institutes of Health Grants CA75253 and CA79683 to L-Z Sun. The pSBE4-Luc plasmid was a kind gift from Dr Bert Vogelstein.

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  1. Department of Cellular & Structural Biology, The University of Texas Health Science Center, San Antonio, 78229, Texas, TX, USA

    Xiufen Lei, Abhik Bandyopadhyay, Thy Le & LuZhe Sun

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Correspondence to LuZhe Sun.

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Lei, X., Bandyopadhyay, A., Le, T. et al. Autocrine TGFβ supports growth and survival of human breast cancer MDA-MB-231 cells. Oncogene 21, 7514–7523 (2002). https://doi.org/10.1038/sj.onc.1205966

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