Expression of Wild-Type and Variant Estrogen Receptor Alpha in Liver Carcinogenesis and Tumor Progression
Expression of Wild-Type and Variant Estrogen Receptor Alpha in Liver Carcinogenesis and Tumor Progression
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DOI：
10.1089/omi.2010.0108
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发表时间：
2011-05-01
影响因子：
3.3
通讯作者：
Carruba, Giuseppe
中科院分区：
文献类型：
--
作者：
Miceli, Vitale;Cocciadiferro, Letizia;Carruba, Giuseppe
尽管雌激素受体（ER）在人肝细胞癌（HCC）中表达，但一些临床试验未能证明抗雌激素治疗HCC患者的疗效。最近，几种ER剪接变异体的鉴定已经揭示了外周组织中雌激素信号传导的复杂性，这可能有助于理解雌激素在非肿瘤或恶性非经典靶器官（包括肝脏）中的作用。在这项工作中，我们研究了mRNA表达的野生型和剪接变异体的ER α在非肿瘤，肝硬化和恶性人类肝脏，以及在肝癌细胞系，使用外显子特异性逆转录聚合酶链反应（RT-PCR）。特别是，ER α 66在非肿瘤组织中检测到，在较小程度上，在肝硬化组织中检测到，而其表达在HCC组织和细胞系中降低或变得不可检测。ER α 46剪接变体在所有样品中均被检测到;然而，有趣的是，ER α 36变体相对于ER α 66反向表达，在HepG 2细胞中最高，在Huh 7细胞中居中，在HA 22 T细胞中最低。值得注意的是，芳香化酶相应地与ER α 36表达，并且与ER α 66负相关。这一观察结果表明，从ER α 66到ER α 36的主要表达的转变可能与人HCC的发生和/或进展有关。
Although estrogen receptors (ERs) are expressed in human hepatocellular carcinoma (HCC), several clinical trials have failed to demonstrate the efficacy of antiestrogen treatment in HCC patients. Recently, the identification of several ER splicing variants has enlightened the complex nature of estrogen signaling in peripheral tissues; this may help understanding estrogen role in either nontumoral or malignant nonclassical target organs, including liver. In this work we have investigated mRNA expression of wild-type and splice variants of ER alpha in nontumoral, cirrhotic, and malignant human liver, as well as in HCC cell lines, using an exon-specific reverse transcription polymerase chain reaction (RT-PCR). In particular, ER alpha 66 was detected in nontumoral and, to a lesser extent, in cirrhotic liver tissues, whereas its expression decreased or became undetectable in HCC tissues and cell lines. The ER alpha 46 splicing variant was detected ubiquitously in all samples; interestingly, however, the ER alpha 36 variant was inversely expressed with respect to ER alpha 66, being highest in HepG2 cells, intermediate in Huh7 cells, and lowest in HA22T cells. It is noteworthy that aromatase was correspondingly expressed with ER alpha 36 and inversely related to ER alpha 66. This observation suggests that a switch from ER alpha 66 to a predominant expression of ER alpha 36 may be associated with development and/or progression of human HCC.