title: 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-NH(2)-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.
authors.affiliation: Department of Cell Genetics, Sasaki Institute, Kanda-Surugadai, Tokoyo 101-0062, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sakurai
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kondoh
authors.forename: Massaki
authors.initials: M
authors.lastname: Arai
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Hamada
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamada
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kihara-Negishi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Izawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohno
authors.forename: Mikio
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Tsuneyuki
authors.initials: T
authors.lastname: Oikawa
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics*; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D019254:Genes, bcl-2 / Q000502:physiology*; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: C098179:FLII protein, human; D008840:Microfilament Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators