Functional roles of Fli‐1, a member of the Ets family of transcription factors, in human breast malignancy

Abstract

The Ets family of transcription factors is implicated in malignant transformation and tumor progression, including invasion, metastasis and neo‐angiogenesis. In the present study, we found that the Fli‐1 gene, a member of the Ets family, was highly expressed in several breast cancer cell lines (MDA‐MB231, MDA‐MB436, BT‐549 and HCC1395). To investigate the functional roles of Fli‐1 in breast cancer malignancy, we introduced an expression plasmid containing full‐length Fli‐1 cDNA into MCF7 breast cancer cells in which endogenous expression of Fli‐1 was barely detectable. Overexpression of Fli‐1 in MCF7 cells led to inhibition of apoptosis induced by serum depletion or ultraviolet irradiation, although it did not affect cell growth rate in liquid media, colony formation in soft agar or the in vitro invasion capacity of the cells. Expression of Fli‐1 and antiapoptotic bcl‐2 was coordinately upregulated by serum depletion in MCF7 cells, and the upregulation was inhibited by treatment of the cells with a c‐Jun–NH₂‐terminal kinase‐specific inhibitor. Furthermore, expression of the bcl‐2 gene and protein was enhanced in Fli‐1‐overexpressing MCF7 cells compared with mock‐transfected cells. In addition, human bcl‐2 promoter activity was transactivated by Fli‐1. These results suggest that Fli‐1 contributes to the malignancy of human breast cancer by inhibiting apoptosis through upregulated expression of the bcl‐2 gene. (Cancer Sci 2007; 98: 1775–1784)