Triple negative breast cancer (TNBC) is categorized by a lack in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 receptor (HER2). TNBC is known to be more aggressive and lethal than other types of breast cancer because of their highly invasive and migratory ability. However, the mechanisms and main contributors of their metastatic ability are still unclear. ETS transcription factors are related with tumorigenesis in many tissues including breast epithelium. Among them, ELF3 (ESX/ESE1) is an epithelial-specific gene that is specifically associated with breast cancer and has been amplified in early breast cancer. The potential role of ELF3 in cytoplasm is presented, but the mechanism of ability to regulate tumor-associated gene expression and breast cell survival for ELF3 are not yet known. Several studies have suggested that the role of EMT is important in the aggressiveness and metastasis of TNBC. It is also known to play an important role in the formation of tumors in most invasive cancer. The main functions of EMT, such as down-regulation of E-cadherin and up-regulation of MMP, are known to be regulated by transcription factors including Snail, Slug and ZEB1.
For investigation of ELF3 ability in TNBC, we performed a series of assays; western blot, wound healing, invasion, soft-agar colony formation, flow cytometry, anoikis, CAM and immunofluorescence assays.
In this study, we found that ELF3, an ETS transcription factor, was expressed low and high in mesenchymal and epithelial type of TNBC cell lines, respectively. Remarkably, overexpressed ELF3 in the highly invasive TNBC cell lines, MDA-MB-231 and BT549, suppressed EMT by attenuating the expression of several EMT-associated proteins (Vimentin, Slug and MMPs). Moreover, ELF3 overexpression reduced the tumor growth of BT549 in chick embryo chorioallantoic membrane (CAM) model.
Although high ELF3 expression has been known to be associated with tumorigenesis of other breast cancer types, overexpression of ELF3 in TNBC suppressed the metastatic potential of invasive TNBC cells. Our results suggest the important role for ELF3 in metastasis of TNBC.
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Ewha Womans University
All authors have declared no conflicts of interest.