Functional roles of Fli-1, a member of the Ets family of transcription factors, in human breast malignancy
Functional roles of Fli-1, a member of the Ets family of transcription factors, in human breast malignancy
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DOI：
10.1111/j.1349-7006.2007.00598.x
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发表时间：
2007-11-01
期刊：
影响因子：
5.7
通讯作者：
Oikawa, Tsuneyuki
中科院分区：
文献类型：
--
作者：
Sakurai, Takuya;Kondoh, Nobuo;Oikawa, Tsuneyuki
转录因子Ets家族参与恶性转化和肿瘤进展，包括侵袭、转移和新血管生成。在本研究中，我们发现Ets家族成员Fli-1基因在几种乳腺癌细胞系（MDA-MB 231、MDA-MB 436、BT-549和HCC 1395）中高度表达。为了研究Fli-1在乳腺癌恶性肿瘤中的功能作用，我们将含有全长Fli-1 cDNA的表达质粒导入MCF 7乳腺癌细胞中，其中Fli-1的内源性表达几乎不可检测。Fli-1在MCF 7细胞中的过表达导致对血清耗竭或紫外线照射诱导的凋亡的抑制，尽管它不影响细胞在液体培养基中的生长速率、软琼脂中的集落形成或细胞的体外侵袭能力。Fli-1和抗凋亡bcl-2的表达通过血清耗竭在MCF 7细胞中协同上调，并且通过用c-Jun-NH 2-末端激酶特异性抑制剂处理细胞来抑制上调。此外，bcl-2基因和蛋白的表达在Fli-1过表达的MCF 7细胞与模拟转染细胞相比，增强。此外，人bcl-2启动子活性被Fli-1反式激活。这些结果表明，Fli-1有助于通过上调bcl-2基因的表达抑制细胞凋亡的人乳腺癌的恶性。
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.