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.
Highlights
Invasive breast adenocarcinoma is the most common cancer in women [1]
We based our present study on the observation that Api5 is overexpressed in breast cancer and correlated to a poor survival outcome of Estrogen Receptor α (ERα) positive breast cancer www.impactjournals.com/oncotarget patients and on a previous study in which it appeared that the nuclear factor Api5 could be a cofactor of ERα [9]
They showed that the presence of Api5 in essential for ERα signalization triggered by E2
Summary
Invasive breast adenocarcinoma is the most common cancer in women [1]. New prognostic markers and molecular targets are developing and present new hopes concerning patient’s management and target therapies in breast cancer. Activation or repression by the estrogen receptor is linked to the availability of coactivators or corepressors and to the genomic context: promoter position of Sp1 and half ERE binding sites, the presence of ERE binding sites or for example the presence of a variant AP-1 binding site [5]. These regulations are complex and it has been proposed a non estrogen mediated stimulation for the estrogen receptor [6]. ERα positive expression is a pathway for breast tumor growth but is associated to good prognostic such as well-differentiated and less invasive tumors
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