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Glypican-3 expression is silenced in human breast cancer

Oncogene volume 20, pages 7408–7412 (2001)Cite this article

Abstract

Glypican-3 (GPC3) is a membrane-bound heparan sulfate proteoglycan that is mutated in the Simpson-Golabi-Behmel syndrome. This is an X-linked condition characterized by overgrowth, and various visceral and skeletal dysmorphisms. The phenotype of the Simpson-Golabi-Behmel syndrome patients and GPC3-deficient mice, as well as gene transfection experiments indicate that GPC3 can act as an inhibitor of cell proliferation and survival. It has been previously shown that GPC3 expression is downregulated in mesotheliomas and ovarian cancer. Here we report that GPC3 expression is also silenced in human breast cancer, and that this silencing is due, at least in part, to hypermethylation of the GPC3 promoter. Ectopic expression of GPC3 inhibited growth in eight out of 10 breast cancer cell lines. Collectively, these data suggest that GPC3 can act as a negative regulator of breast cancer growth.

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Acknowledgements

We thank Penny Papadakos for assistance in the preparation of this manuscript. This work has been supported by the Canadian Breast Cancer Research Initiative, the Canadian Institutes for Health Research and the Sunnybrook Trust for Medical Research.

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Authors and Affiliations

  1. Sunnybrook and Women's College Health Sciences Centre, Molecular and Cell Biology Research Program, 2075 Bayview Avenue, Toronto, M4N 3M5, Ontario, Canada

    Yun-Yan Xiang, Virginia Ladeda & Jorge Filmus

  2. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

    Yun-Yan Xiang, Virginia Ladeda & Jorge Filmus

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  1. Yun-Yan Xiang
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  2. Virginia Ladeda
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Correspondence to Jorge Filmus.

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Xiang, YY., Ladeda, V. & Filmus, J. Glypican-3 expression is silenced in human breast cancer. Oncogene 20, 7408–7412 (2001). https://doi.org/10.1038/sj.onc.1204925

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