https://scholars.lib.ntu.edu.tw/handle/123456789/568641
標題: | Hepatitis B virus X protein enhances androgen receptor-responsive gene expression depending on androgen level | 作者: | Chiu C.-M. Shiou-Hwei Yeh PEI-JER CHEN Kuo T.-J. Chang C.-J. Yang W.-J. DING-SHINN CHEN |
關鍵字: | Androgen-responsive element | 公開日期: | 2007 | 出版社: | National Academy of Sciences | 卷: | 104 | 期: | 8 | 起(迄)頁: | 2571-2578 | 來源出版物: | Proceedings of the National Academy of Sciences of the United States of America | 摘要: | Persistent hepatitis B virus (HBV) infection is a major risk of hepatocellular carcinoma (HCC). One intriguing feature of HBV-related HCC is the male predominance, with a male to female ratio of 5-7:1. This dominance has been attributed to the elevated androgen level and the enhanced androgen receptor (AR)-mediated activity in the host. How HBV infection and AR signaling modulate HCC is unknown. We investigated whether the HBV nonstructural protein, X protein (HBx) could cooperate with the AR signaling pathway to enhance carcinogenesis. We found that HBx increased the anchorage-independent colony-formation potency of AR in a non transformed mouse hepatocyte cell line. We also found that HBx functioned as a positive transcriptional coregulator to increase AR-mediated transcriptional activity. This transcription enhancement was increased in the presence of androgen in a concentration-responsive manner, thus explaining a more prominent effect in males. HBx did not physically associate with ligand-bound AR in the nucleus, and it likely augmented AR activity by increasing the phosphorylation of AR through HBx-mediated activation of the c-Src kinase signaling pathway. Our study documents HBx as a previously undescribed class of noncellular positive coregulators for AR. The results reveal a mechanism for the vulnerability of males to microbial infections and the subsequent development of cancer. ? 2007 by The National Academy of Sciences of the USA. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984548383&doi=10.1073%2fpnas.0609498104&partnerID=40&md5=1b405ffd98fd0f24aece103b8d3a26c4 https://scholars.lib.ntu.edu.tw/handle/123456789/568641 |
ISSN: | 0027-8424 | DOI: | 10.1073/pnas.0609498104 | SDG/關鍵字: | 2 morpholino 8 phenylchromone; 4 amino 7 tert butyl 5 (4 chlorophenyl)pyrazolo[3,4 d]pyrimidine; androgen receptor; androstanolone; anthra[1,9 cd]pyrazol 6(2h) one; cyclosporin A; hepatitis B virus X protein; luciferase; metribolone; mitogen activated protein kinase inhibitor; protein kinase; uo 126; virus protein; anchorage independent growth; animal cell; apoptosis; article; calcium cell level; cancer risk; cell strain MCF 7; chronic hepatitis; disease predisposition; gene expression; genetic transcription; hepatitis B; Hepatitis B virus; hepatoma cell; hormone responsive element; human; human cell; immunoprecipitation; ligand binding; liver carcinogenesis; liver cell carcinoma; liver cell culture; liver cirrhosis; mouse; nonhuman; priority journal; protein analysis; sex difference; virus hepatitis; Western blotting; Hepatitis B virus |
顯示於: | 臨床醫學研究所 |
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