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The docking protein Gab2 is overexpressed and estrogen regulated in human breast cancer

Oncogene volume 21, pages 5175–5181 (2002)Cite this article

Abstract

Grb2-associated binder 2 (Gab2) is a recently identified member of the Gab/Daughter of sevenless family of docking proteins, which localize, amplify and integrate signaling pathways activated by various receptors including receptor tyrosine kinases (RTKs). To date, Gab2 signaling has been primarily investigated in hematopoietic cells. Here we report marked overexpression of Gab2 in a subset of breast cancer cell lines relative to normal breast epithelial strains and a trend for increased Gab2 expression in estrogen receptor (ER)-positive lines. Overexpression relative to normal ductal epithelium was also observed in some primary breast cancers. In MCF-7 breast cancer cells Gab2 was markedly tyrosine phosphorylated in response to heregulin and also following EGF, insulin or bFGF administration, indicating that a variety of RTKs implicated in breast cancer development or progression couple to this docking protein. In hormone-responsive breast cancer cells, GAB2 mRNA and protein expression were induced by estradiol in a manner sensitive to the pure anti-estrogen ICI 182780, indicating that this regulation is mediated via the ER. Gab2 therefore represents a novel link between steroid and growth factor signaling in breast cancer, and when overexpressed, may modulate the sensitivity of breast cancer cells to these important growth regulators.

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Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia, the Cancer Council New South Wales. NIH grants ca49152 and 66600 (to BG Neel) and an American Association for Cancer Research Fellowship (to H= Gu), ICI 182780 was a kind gift of Dr Alan Wakeling, AstraZeneca Pharmaceuticals, Alderley Park, Cheshire, UK.

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Authors and Affiliations

  1. Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, 2010, NSW, Australia

    Roger J Daly, Jayamala Parmar, Suzann Malaney, Ruth J Lyons, Rania Kairouz, Darren R Head, Susan M Henshall & Robert L Sutherland

  2. Division of Hematology and Oncology, Department of Medicine, Cancer Biology Program, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 02215, Massachusetts, MA, USA

    Haihua Gu & Benjamin G Neel

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  1. Roger J Daly
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Correspondence to Roger J Daly.

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Daly, R., Gu, H., Parmar, J. et al. The docking protein Gab2 is overexpressed and estrogen regulated in human breast cancer. Oncogene 21, 5175–5181 (2002). https://doi.org/10.1038/sj.onc.1205522

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