Dual Function of ERRα in Breast Cancer and Bone Metastasis Formation: Implication of VEGF and Osteoprotegerin
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- Anaïs Fradet
- Authors' Affiliations: 1Inserm, UMR1033; 2University of Lyon; 3Centre hospitalier Lyon Sud, Lyon, France; 4University of Liège, Liège, Belgique; and 5University of Toronto, Toronto, Canada
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- Helène Sorel
- Authors' Affiliations: 1Inserm, UMR1033; 2University of Lyon; 3Centre hospitalier Lyon Sud, Lyon, France; 4University of Liège, Liège, Belgique; and 5University of Toronto, Toronto, Canada
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- Lamia Bouazza
- Authors' Affiliations: 1Inserm, UMR1033; 2University of Lyon; 3Centre hospitalier Lyon Sud, Lyon, France; 4University of Liège, Liège, Belgique; and 5University of Toronto, Toronto, Canada
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- Delphine Goehrig
- Authors' Affiliations: 1Inserm, UMR1033; 2University of Lyon; 3Centre hospitalier Lyon Sud, Lyon, France; 4University of Liège, Liège, Belgique; and 5University of Toronto, Toronto, Canada
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- Baptiste Dépalle
- Authors' Affiliations: 1Inserm, UMR1033; 2University of Lyon; 3Centre hospitalier Lyon Sud, Lyon, France; 4University of Liège, Liège, Belgique; and 5University of Toronto, Toronto, Canada
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- Akeila Bellahcène
- Authors' Affiliations: 1Inserm, UMR1033; 2University of Lyon; 3Centre hospitalier Lyon Sud, Lyon, France; 4University of Liège, Liège, Belgique; and 5University of Toronto, Toronto, Canada
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- Vincent Castronovo
- Authors' Affiliations: 1Inserm, UMR1033; 2University of Lyon; 3Centre hospitalier Lyon Sud, Lyon, France; 4University of Liège, Liège, Belgique; and 5University of Toronto, Toronto, Canada
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- Hélène Follet
- Authors' Affiliations: 1Inserm, UMR1033; 2University of Lyon; 3Centre hospitalier Lyon Sud, Lyon, France; 4University of Liège, Liège, Belgique; and 5University of Toronto, Toronto, Canada
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- Françoise Descotes
- Authors' Affiliations: 1Inserm, UMR1033; 2University of Lyon; 3Centre hospitalier Lyon Sud, Lyon, France; 4University of Liège, Liège, Belgique; and 5University of Toronto, Toronto, Canada
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- Jane E. Aubin
- Authors' Affiliations: 1Inserm, UMR1033; 2University of Lyon; 3Centre hospitalier Lyon Sud, Lyon, France; 4University of Liège, Liège, Belgique; and 5University of Toronto, Toronto, Canada
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- Philippe Clézardin
- Authors' Affiliations: 1Inserm, UMR1033; 2University of Lyon; 3Centre hospitalier Lyon Sud, Lyon, France; 4University of Liège, Liège, Belgique; and 5University of Toronto, Toronto, Canada
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- Edith Bonnelye
- Authors' Affiliations: 1Inserm, UMR1033; 2University of Lyon; 3Centre hospitalier Lyon Sud, Lyon, France; 4University of Liège, Liège, Belgique; and 5University of Toronto, Toronto, Canada
説明
<jats:title>Abstract</jats:title> <jats:p>Bone metastasis is a complication occurring in up to 70% of advanced breast cancer patients. The estrogen receptor-related receptor alpha (ERRα) has been implicated in breast cancer and bone development, prompting us to examine whether ERRα may function in promoting the osteolytic growth of breast cancer cells in bone. In a mouse xenograft model of metastatic human breast cancer, overexpression of wild-type ERRα reduced metastasis, whereas overexpression of a dominant negative mutant promoted metastasis. Osteoclasts were directly affected and ERRα upregulated the osteoclastogenesis inhibitor, osteoprotegerin (OPG), providing a direct mechanistic basis for understanding how ERRα reduced breast cancer cell growth in bone. In contrast, ERRα overexpression increased breast cancer cell growth in the mammary gland. ERRα-overexpressing primary tumors were highly vascularized, consistent with an observed upregulation of angiogenic growth factor, the VEGF. In support of these findings, we documented that elevated expression of ERRα mRNA in breast carcinomas was associated with high expression of OPG and VEGF and with disease progression. In conclusion, our results show that ERRα plays a dual role in breast cancer progression in promoting the local growth of tumor cells, but decreasing metastatic growth of osteolytic lesions in bone. Cancer Res; 71(17); 5728–38. ©2011 AACR.</jats:p>
収録刊行物
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- Cancer Research
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Cancer Research 71 (17), 5728-5738, 2011-08-30
American Association for Cancer Research (AACR)