Estrogen receptor expression in chronic hepatitis C and hepatocellular carcinoma pathogenesis.
Estrogen receptor expression in chronic hepatitis C and hepatocellular carcinoma pathogenesis.
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DOI：
10.3748/wjg.v23.i37.6802
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发表时间：
2017-10-07
影响因子：
4.3
通讯作者：
Kaul R
中科院分区：
文献类型：
--
作者：
Iyer JK;Kalra M;Kaul A;Payton ME;Kaul R
目的探讨雌激素受体（ER）在正常人、丙型肝炎（HCV）相关肝硬化和肝细胞癌（HCC）患者中的表达。从NIH肝脏组织和细胞分布系统获得来自正常供体和诊断为HCV相关肝硬化和HCV相关HCC的患者的肝脏组织。Western blotting和real-time RT-PCR检测ERα和ERβ的表达。通过Western blotting和免疫组化进一步确定ERα和ERβ在细胞核和细胞质组织裂解物中的亚细胞分布沿着炎性[活化的NF-κB和Iκ B-激酶（IKK）]和致癌（细胞周期蛋白D1）标志物的表达。ERα、ERβ表达与活化的NF-κB、IKK和cyclin D1表达呈斯皮尔曼相关。ER α和ER β在正常肝组织中均有表达，但男性ERα的表达明显高于女性（P < 0.05）。HCV相关性肝癌组织中ERα mRNA表达显著高于正常肝组织（P < 0.05），HCV相关性肝硬化和HCV相关性肝癌组织中ERβ mRNA表达显著高于正常肝组织（P < 0.05）。在蛋白水平上，HCV相关性HCC患者肝细胞核ERα和HCV相关性肝硬化患者肝细胞核ERβ的表达均显著高于正常人（P < 0.05）。此外，我们还观察到磷酸化NF-κB和cyclin D1在病变肝脏中的表达显著增加（P < 0.05）。在HCV相关的HCC肝组织中，细胞核ER亚型与细胞核cyclin D1的表达呈正相关，细胞质ER亚型与细胞质磷酸化IKK的表达呈负相关。这些发现表明，慢性HCV感染后ER亚型的表达失调可能有助于HCV相关肝硬化向HCV相关HCC的进展。ERα在正常肝组织中的表达存在性别差异。在病变肝脏中观察到的ER亚型表达的改变可能影响HCV相关发病机制中的性别差异。
To investigate gender-specific liver estrogen receptor (ER) expression in normal subjects and patients with hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma (HCC). Liver tissues from normal donors and patients diagnosed with HCV-related cirrhosis and HCV-related HCC were obtained from the NIH Liver Tissue and Cell Distribution System. The expression of ER subtypes, ERα and ERβ, were evaluated by Western blotting and real-time RT-PCR. The subcellular distribution of ERα and ERβ was further determined in nuclear and cytoplasmic tissue lysates along with the expression of inflammatory [activated NF-κB and IκB-kinase (IKK)] and oncogenic (cyclin D1) markers by Western blotting and immunohistochemistry. The expression of ERα and ERβ was correlated with the expression of activated NF-κB, activated IKK and cyclin D1 by Spearman’s correlation. Both ER subtypes were expressed in normal livers but male livers showed significantly higher expression of ERα than females (P < 0.05). We observed significantly higher mRNA expression of ERα in HCV-related HCC liver tissues as compared to normals (P < 0.05) and ERβ in livers of HCV-related cirrhosis and HCV-related HCC subjects (P < 0.05). At the protein level, there was a significantly higher expression of nuclear ERα in livers of HCV-related HCC patients and nuclear ERβ in HCV-related cirrhosis patients as compared to normals (P < 0.05). Furthermore, we observed a significantly higher expression of phosphorylated NF-κB and cyclin D1 in diseased livers (P < 0.05). There was a positive correlation between the expression of nuclear ER subtypes and nuclear cyclin D1 and a negative correlation between cytoplasmic ER subtypes and cytoplasmic phosphorylated IKK in HCV-related HCC livers. These findings suggest that dysregulated expression of ER subtypes following chronic HCV-infection may contribute to the progression of HCV-related cirrhosis to HCV-related HCC. Gender differences were observed in ERα expression in normal livers. Alterations in ER subtype expression observed in diseased livers may influence gender-related disparity in HCV-related pathogenesis.
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影响因子：
5.4
作者：
Bidell MR;McLaughlin M;Faragon J;Morse C;Patel N
通讯作者：
Patel N
影响因子：
4.1
作者：
Klinge, Carolyn M.;Riggs, Krista A.;Wickramasinghe, Nalinie S.;Emberts, Celia G.;McConda, David B.;Barry, Parul N.;Magnusen, Joan E.
通讯作者：
Magnusen, Joan E.
影响因子：
50.5
作者：
Liedtke, C.;Broglio, K.;Gonzalez-Angulo, A. M.
通讯作者：
Gonzalez-Angulo, A. M.
影响因子：
2.6
作者：
Hayashida, Kazumi;Shoji, Ikuo;Hotta, Hak
通讯作者：
Hotta, Hak
影响因子：
3.8
作者：
Hillung, Julia;Ruiz-Lopez, Elena;Mas, Antonio
通讯作者：
Mas, Antonio