Reference : Dual function of ERR alpha in breast cancer and bone metastasis formation: implicatio...
Scientific journals : Article
Human health sciences : Oncology
Life sciences : Biochemistry, biophysics & molecular biology
Dual function of ERR alpha in breast cancer and bone metastasis formation: implication of VEGF and osteoprotegerin.
Fradet, Anais [> >]
Sorel, Helene [> >]
Bouazza, Lamia [> >]
Goehrig, Delphine [> >]
Depalle, Baptiste [> >]
Bellahcene, Akeila mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Castronovo, Vincenzo mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
Follet, Helene [> >]
Descotes, Francoise [> >]
Aubin, Jane E. [> >]
Clezardin, Philippe [> >]
Bonnelye, Edith [> >]
Cancer Research
American Association for Cancer Research, Inc. (AACR)
Yes (verified by ORBi)
United States
[en] Animals ; Bone Neoplasms/metabolism/mortality/secondary ; Breast Neoplasms/blood supply/metabolism/pathology ; Carcinoma/blood supply/metabolism/secondary ; Cell Line, Tumor ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Neovascularization, Pathologic/genetics/metabolism ; Osteoprotegerin/metabolism ; Receptors, Estrogen/biosynthesis/genetics ; Vascular Endothelial Growth Factor A/metabolism ; Xenograft Model Antitumor Assays
[en] Bone metastasis is a complication occurring in up to 70% of advanced breast cancer patients. The estrogen receptor-related receptor alpha (ERRalpha) has been implicated in breast cancer and bone development, prompting us to examine whether ERRalpha 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 ERRalpha reduced metastasis, whereas overexpression of a dominant negative mutant promoted metastasis. Osteoclasts were directly affected and ERRalpha upregulated the osteoclastogenesis inhibitor, osteoprotegerin (OPG), providing a direct mechanistic basis for understanding how ERRalpha reduced breast cancer cell growth in bone. In contrast, ERRalpha overexpression increased breast cancer cell growth in the mammary gland. ERRalpha-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 ERRalpha mRNA in breast carcinomas was associated with high expression of OPG and VEGF and with disease progression. In conclusion, our results show that ERRalpha 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.
CNRS (EB), INSERM, The University of Lyon ; Ligue Régionale contre le cancer ; Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS

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