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Y盒结合蛋白dbpA的转录受E2F1正向调控:对肝癌发生的影响

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

作者信息

Arakawa Yasuo, Kajino Kazunori, Kano Sayaka, Tobita Hiroshi, Hayashi Junpei, Yasen Mahamute, Moriyama Mitsuhiko, Arakawa Yasuyuki, Hino Okio

机构信息

Department of Experimental Pathology, Cancer Institute, Japanese Fundation of Cancer Research, Tokyo, Japan.

出版信息

Biochem Biophys Res Commun. 2004 Sep 10;322(1):297-302. doi: 10.1016/j.bbrc.2004.04.208.

Abstract

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.

摘要

人类肝细胞癌是世界上最常见的癌症之一。我们之前表明,Y盒蛋白家族成员dbpA可加速炎症诱导的肝癌发生过程,且dbpA在肝细胞癌中的表达比在非肿瘤组织中更为丰富。在本研究中,为阐明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。我们关注了与E2F结合位点相似的序列5'-TTTGGGGC-3'(启动子区域中-8至-1位)(一个碱基错配,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,而通过对该序列进行突变或缺失,这种增加被消除。因此,dbpA的表达受E2F1正向调控,这表明E2F1对细胞增殖的作用之一可能在致癌步骤由dbpA介导。

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