Api5 a new cofactor of estrogen receptor alpha involved in breast cancer outcome

Céline Basset; Florence Bonnet-Magnaval; Marina Garcia-Jove Navarro; Christian Touriol; Monique Courtade; Hervé Prats; Barbara Garmy-Susini; Eric Lacazette

doi:10.18632/oncotarget.17281

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Research Papers:

Api5 a new cofactor of estrogen receptor alpha involved in breast cancer outcome

Céline Basset, Florence Bonnet-Magnaval, Marina Garcia-Jove Navarro, Christian Touriol, Monique Courtade, Hervé Prats, Barbara Garmy-Susini and Eric Lacazette _

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Oncotarget. 2017; 8:52511-52526. https://doi.org/10.18632/oncotarget.17281

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Abstract

Céline Basset1,3, Florence Bonnet-Magnaval2, Marina Garcia-Jove Navarro2, Christian Touriol1, Monique Courtade1,3, Hervé Prats1, Barbara Garmy-Susini2 and Eric Lacazette2

1U1037-CRCT, INSERM, Université Toulouse, F-31037, Toulouse, France

2UMR 1048-I2MC, INSERM, Université Toulouse, F-31432, Toulouse, France

3Laboratoire d’Histologie-Embryologie, Faculté de Médecine Rangueil, F-31062, Toulouse, France

Correspondence to:

Eric Lacazette, email: [email protected]

Keywords: breast cancer, apoptosis inhibitor 5, estrogen receptor alpha, co-factor, tumorigenesis

Received: June 30, 2016 Accepted: March 10, 2017 Published: April 20, 2017

ABSTRACT

Api5 (Apoptosis inhibitor 5) is an anti-apoptotic factor that confers resistance to genotoxic stress in human cancer. Api5 is also expressed in endothelial cells and participates to the Estrogen Receptor α (ERα) signaling to promote cell migration. In this study, we found an over expression of Api5 in human breast cancer. Given that we show that high expression of Api5 in breast cancer patients is associated with shorter recurrence free survival, we investigated the relationship between ERα and Api5 at the molecular level. We found that Api5 Nuclear Receptor box (NR box) drives a direct interaction with the C domain of ERα. Furthermore, Api5 participates to gene transcription activation of ERα target genes upon estrogen treatment. Besides, Api5 expression favors tumorigenicity and migration and is necessary for tumor growth in vivo in mice xenografted model of breast cancer cell line. These finding suggest that Api5 is a new cofactor of ERα that functionally participates to the tumorigenic phenotype of breast cancer cells. In ERα breast cancer patients, Api5 overexpression is associated with poor survival, and may be used as a predictive marker of breast cancer recurrence free survival.

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Research Papers:

Api5 a new cofactor of estrogen receptor alpha involved in breast cancer outcome

Abstract