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GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis

Oncogene volume 28, pages 2634–2642 (2009)Cite this article

Abstract

The loss of expression of the transcription factor GATA3 in breast tumors has been linked to aggressive tumor development and poor patient survival. In the present work, we address potential roles for GATA3 in breast tumor lung metastasis and progression. Using an aggressive breast cancer cell line, which metastasizes specifically to the lung, we show that GATA3 expression results in reduced tumor outgrowth in the mammary fat pad and lower lung metastatic burden in nude mice. Specifically, GATA3 expression inhibits breast cancer cell expansion inside the lung parenchyma. This phenotype correlates with the ability of GATA3 to negatively regulate the expression of several genes that promote breast cancer lung metastasis (ID1/-3, KRTHB1, LY6E and RARRES3). Conversely, the expression of genes encoding known inhibitors of lung metastasis (DLC1 (deleted in liver cancer 1) and PAEP (progestagen-associated endometrial protein)) is upregulated by GATA3. These data correlate with microarray data from human breast cancer patients, showing a strong correlation between high GATA3 expression and absence of metastases specifically to the lungs. We conclude that GATA3 inhibits primary breast tumor outgrowth and reduces lung metastatic burden by regulating key genes involved in metastatic breast tumor progression.

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Abbreviations

ER:

estrogen receptor-α

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Acknowledgements

The authors are grateful to Dr Perou (Division of Cancer Epidemiology and Genetics, the National Cancer Institute, MD 20852-7234, USA) for sharing cDNA constructs. The work was supported by the Canadian Institutes for Health Research grant MOP-84470 and a Canderel New Initiative Award to MB. ABD was supported by a fellowship from the Carlsberg Foundation (2006_01_0102) and a Canadian Institutes for Health Research Cancer Consortium Training Grant Fellowship Award. AANR is supported by a studentship from the Fonds de la Recherche en Santé du Québec. PS is a research scientist of the National Cancer Institute of Canada. MB holds a Canada Research Chair in Developmental Genetics of the Urogenital System.

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Authors and Affiliations

  1. Biochemistry Department, Goodman Cancer Centre, McGill University, Montreal, Quebec, Canada

    A B Dydensborg, A A N Rose, B J Wilson, D Grote, V Giguère, P M Siegel & M Bouchard

  2. Department of Medicine, Comparative Pathology Facility, McGill University, Montreal, Quebec, Canada

    M Paquet

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  1. A B Dydensborg
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  2. A A N Rose
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  3. B J Wilson
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  4. D Grote
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  6. V Giguère
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  7. P M Siegel
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  8. M Bouchard
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Correspondence to M Bouchard.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Dydensborg, A., Rose, A., Wilson, B. et al. GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis. Oncogene 28, 2634–2642 (2009). https://doi.org/10.1038/onc.2009.126

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