https://scholars.lib.ntu.edu.tw/handle/123456789/568564
標題: | Gender disparity of hepatocellular carcinoma: The roles of sex hormones | 作者: | Shiou-Hwei Yeh PEI-JER CHEN |
關鍵字: | Androgen; Androgen receptor; Estrogen; Estrogen receptor; Hepatitis B virus; Hepatocellular carcinoma | 公開日期: | 2010 | 出版社: | S. Karger AG | 卷: | 78 | 期: | SUPPL. 1 | 起(迄)頁: | 172-179 | 來源出版物: | Oncology | 摘要: | Men have a higher incidence of hepatocellular carcinoma (HCC) than women. Epidemiologic and animal studies have suggested that it might be due to the stimulatory effects of androgen and the protective effects of estrogen. Recently, increasing molecular mechanisms underlying the carcinogenic effect of both sex hormones were reported. Knockout of androgen receptor (AR) expression in hepatocytes delayed the development of N′,N′-diethylnitrosamine (DEN)-induced HCC, suggesting the active AR pathway in augmenting the HCC risk. Moreover, an intriguing interaction between the viral protein of hepatitis B virus X protein (HBx) and the androgen pathway was established. HBx can enhance the transcriptional activity of AR in a ligand concentration-dependent manner, mainly through its effects on the c-Src and GSK-3β kinase pathways. The studies from the DEN-induced HCC mouse model further provided a mechanism for the protective role of estrogen in female HCC. Estrogen can protect hepatocytes from malignant transformation via downregulation of IL-6 release from Kupffer cells, a critical process in this mouse model. Intriguingly, suppression of the ERα protein by overexpression of miR-18a, which occurs preferentially in female HCC, was identified as a novel mechanism to block the tumor-protective function of estrogen in female HCC. In conclusion, the current studies demonstrated that the gender disparity of HCC is attributed by both androgen and estrogen sex hormone pathways, with distinct roles in each gender. Therefore, the ligand and the receptor factors of both sex hormones need to be included for assessing the relative risk of HCC patients of each gender. Copyright ? 2010 S. Karger AG. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984568904&doi=10.1159%2f000315247&partnerID=40&md5=b70b3645b248af2c8f4f4d91b058426a https://scholars.lib.ntu.edu.tw/handle/123456789/568564 |
ISSN: | 0030-2414 | DOI: | 10.1159/000315247 | SDG/關鍵字: | androgen; androgen receptor; diethylnitrosamine; estrogen; estrogen receptor alpha; glycogen synthase kinase 3beta; hepatitis B virus X protein; interleukin 6; sex hormone; animal model; cancer risk; carcinogenesis; chronic hepatitis; concentration response; cytokine release; gene overexpression; genetic transcription; human; Kupffer cell; liver cell carcinoma; malignant transformation; mouse; nonhuman; priority journal; receptor down regulation; review; sex difference |
顯示於: | 臨床醫學研究所 |
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