Expression of the E2F family of transcription factors and its clinical relevance in ovarian cancer
Expression of the E2F family of transcription factors and its clinical relevance in ovarian cancer
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DOI：
10.1196/annals.1378.073
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发表时间：
2006-01-01
期刊：
影响因子：
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通讯作者：
Zeimet, Alain G.
中科院分区：
文献类型：
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作者：
Reimer, Daniel;Sadr, Susann;Zeimet, Alain G.
转录因子E2 F家族在细胞增殖的调节中起着关键作用。基于序列同源性和功能，迄今已区分出E2 F转录因子的八个不同成员（E2 F-1至E2 F-8）。E2 F转录因子的调节与视网膜母细胞瘤肿瘤抑制因子家族（RB途径）的功能密切相关。在过去的十年中，发现RB-E2 F通路的不同组分的各种改变与肿瘤进展相关。然而，在卵巢癌的肿瘤生物学中没有关于E2 F家族成员作用的数据。在这里，我们描述了E2 F转录因子在各种人卵巢癌细胞系的表达研究，其临床相关性进行了检查，在77例卵巢癌患者的训练集。与人腹膜间皮细胞（HPMCs）相比，E2 F-1，E2 F-2和E2 F-8的表达水平在所有研究的卵巢癌细胞系中均升高。有趣的是，EGF处理显示转录激活因子E2 F-3的时间依赖性上调，并且E2 F-3的异二聚体伴侣DP-1的同时增加。E2 F-1、E2 F-2和E2 F-8的高表达被发现与卵巢癌患者的组织病理学3级肿瘤和原发性减积手术后直径超过2cm的残留肿瘤相关。总之，这些数据表明，增殖促进E2 F转录因子E2 F-1，特别是E2 F-2在卵巢癌的肿瘤生物学中起着关键作用，并可能成为特异性治疗靶点的候选者。
The E2F family of transcription factors plays a pivotal role in the regulation of cellular proliferation. On the basis of sequence homology and function, eight distinct members of E2F transcription factors (E2F-1 to E2F-8) have been distinguished to date. The regulation of E2F transcription factors is closely associated with the function of the retinoblastoma family of tumor suppressors (RB pathway). In the last decade various alterations of distinct components of the RB-E2F pathway were found to be associated with tumor progression. However, no data on the role of E2F family members are available in tumor biology of ovarian cancer. Here we describe an expression study of E2F transcription factors in various human ovarian cancer cell lines; its clinical relevance was examined in a training set of 77 ovarian cancer patients. Expression levels of E2F-1, E2F-2, and E2F-8 were elevated in all the ovarian cancer cell lines studied when compared with human peritoneal mesothelial cells (HPMCs). Interestingly, EGF treatment showed a time-dependent upregulation of the activating transcription factor E2F-3 and a simultaneous increase of DP-1, the heterodimeric partner of E2F-3. High expression of E2F-1, E2F-2, and E2F-8 was found to be associated with histopathologic grade 3 tumors and residual tumor over 2 cm in diameter after primary debulking surgery in ovarian cancer patients. Taken together, these data suggest that the proliferation-promoting E2F transcription factors E2F-1 and especially E2F-2 play a pivotal role in tumor biology of ovarian cancer and may be candidates for specific therapeutic targets.