Expression of Apoptosis- and Vitamin D Pathway-Related Genes in Hepatocellular Carcinoma
Expression of Apoptosis- and Vitamin D Pathway-Related Genes in Hepatocellular Carcinoma
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DOI：
10.1159/000348441
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发表时间：
2013-01-01
期刊：
影响因子：
3.2
通讯作者：
Canbay, Ali
中科院分区：
文献类型：
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作者：
Fingas, Christian D.;Altinbas, Akif;Canbay, Ali
背景/目的：肝细胞癌是全球第六大常见恶性肿瘤，治疗方案很少。由于它们可能是未来癌症治疗的靶点，因此凋亡相关基因在肝细胞癌中的表达尤其令人感兴趣。在这项先导性研究中，我们进一步研究了人肝细胞癌中与凋亡相关的基因，并将重点放在维生素D信号上，因为它可能是肝细胞癌细胞凋亡的调节因子。方法：我们采用62例肝细胞癌患者和62例健康对照的肿瘤组织和血清样本进行研究。采用定量RT-PCR、免疫组织化学和ELISA法对组织和血清标本进行分析。结果：与正常对照组相比，肝细胞癌患者肝组织中细胞凋亡标记物M30表达升高，多种促凋亡基因(TRAIL、FasL、FasR)和抗凋亡基因(Mcl-1、Bcl2)表达同时上调。此外，与健康肝脏相比，肝癌患者血清维生素D水平降低，而肿瘤组织和肿瘤周围组织维生素D受体mRNA表达增加。结论：在人肝细胞癌中，M30血清水平升高，表明细胞周转增加。调节维生素D途径可能是一种支持性的、促凋亡的肝细胞癌治疗方法。版权所有(C)2013 S.Karger AG，巴塞尔
Background/Aims: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and therapeutic options are scarce. As they might represent future targets for cancer therapy, the expression of apoptosis-related genes in HCC is of particular interest. In this pilot study, we further examined apoptosis-related genes in human HCC and also focused on vitamin D signaling as this might be a regulator of HCC cell apoptosis. Methods: We employed tumor tissue and serum samples from 62 HCC patients as well as 62 healthy controls for these studies. Tissue and serum specimens were analyzed by quantitative RT-PCR, immunohistochemistry and ELISA. Results: In HCC patients the apoptosis marker M30 was found to be elevated and several pro-apoptotic (TRAIL, FasL and FasR) as well as anti-apoptotic genes (Mcl-1 and Bcl-2) were simultaneously up-regulated in tumor tissue and especially tumor-surrounding tissue as compared to healthy control livers. Moreover, vitamin D serum levels were decreased in HCC patients whereas vitamin D receptor mRNA expression was increased in tumor tissue and tumor-surrounding tissue as compared to healthy livers. Conclusions: In human HCC, M30 serum levels are elevated indicating an increased cell turnover. Modulation of the vitamin D pathway might be a supportive, pro-apoptotic HCC therapy. Copyright (C) 2013 S. Karger AG, Basel