Transcription of dbpA, a Y box binding protein, is positively regulated by E2F1: implications in hepatocarcinogenesis

Transcription of dbpA, a Y box binding protein, is positively regulated by E2F1: implications in hepatocarcinogenesis
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DOI:
10.1016/j.bbrc.2004.04.208
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发表时间:
2004-09-10
影响因子:
3.1
通讯作者:
Hino, O
Hino, O
中科院分区:
生物学4区
文献类型:
--
作者:
Arakawa, Y;Kajino, K;Hino, O

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人类肝细胞癌是世界上最常见的癌症之一。我们之前的研究表明,作为Y box蛋白家族的一员,dbpA可以加速炎症诱导的肝癌发生过程,并且dbpA在肝细胞癌中的表达比在非肿瘤组织中的表达更丰富。在本研究中,为了阐明dbpA在增殖状态下表达增强的机制,我们检测了dbpA启动子区域的转录活性。我们重点研究了与E2F结合位点相似的序列5'-TTTGGGGC-3'(启动子区域-8至-1)(1个碱基错配,TFSEARCH评分86.2)。通过在Huh-7细胞中过表达E2F1, dbpA的转录活性显著增加,这种增加可以通过突变或删除该序列来消除。因此,dbpA的表达受到E2F1的正调控,提示E2F1对细胞增殖的影响之一可能是dbpA在癌变过程中介导的。(C) 2004爱思唯尔公司版权所有。
Human hepatocellular carcinoma is one of the most common cancers in the world. We previously showed that dbpA, a member of the Y box family of proteins, could Accelerate the process of inflammation-induced hepatocarcinogenesis, and that dbpA is more abundantly expressed in hepatocellular carcinoma than in non-tumorous tissue. In this study, to clarify the mechanism by which expression of dbpA is enhanced in the proliferative state, we examined the transcriptional activity of the dbpA promoter region. We focused on the sequence 5'-TTTGGGGC-3' (-8 to -1 in the promoter region) resembling the E2F binding site (one base mismatch, TFSEARCH score 86.2). By overexpressing E2F1 in Huh-7 cells, transcriptional activity of dbpA was significantly increased, and this increase was abolished by mutating or deleting this sequence. Thus, expression of dbpA was positively regulated by E2F1, suggesting that one of the effects of E2F1 on cell proliferation might be mediated by dbpA at the carcinogenesis step. (C) 2004 Elsevier Inc. All rights reserved.