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人结肠直肠癌中Sigma1受体基因表达水平的改变。

Altered expression level of Sigma1 receptor gene in human colorectal cancer.

作者信息

Skrzycki Michał, Czeczot Hanna

机构信息

Department of Biochemistry, Warsaw Medical University , Warsaw , Poland.

出版信息

J Recept Signal Transduct Res. 2013 Oct;33(5):313-8. doi: 10.3109/10799893.2013.822891. Epub 2013 Aug 1.

DOI:10.3109/10799893.2013.822891
PMID:23906352
Abstract

Nonopioid Sigma1 receptor (Sig1R) influences numerous metabolism functions including regulation of ion channels, reaction on stress and response to growth signals. Due to this influence, Sigma1 receptor ligands show anti-proliferative and cytotoxic action on tumor cells. Additionally its increased level is observed in some types of tumors. Colorectal cancer is one of the most common cancers worldwide and its clinical development is well described. The aim of the study was evaluation of Sigma1 receptor mRNA expression level in human colorectal cancer and colorectal cancer liver metastases at different stages of tumor development. The mRNA was isolated from 30 patients: 18 with colorectal cancer (CRC) and 12 with colorectal cancer liver metastases (CRCLM). The cDNA of Sig1R gene was amplified by polymerase chain reaction using specific primers. The level of Sig1R mRNA expression was determined by measurement of optical density. Sig1R expression level was increased in CRC and CRCLM. The highest level of Sig1R mRNA was observed in UICC stage III. We also showed significant interactions of UICC stage and tumor localization with Sig1R expression level. There were no interactions between UICC stage and age of patients, although we observed significantly decreased level of Sig1R mRNA in older patients. Clinical advancement stage, localization of tumor and age of patients seems to be an important factors influencing Sigma1 receptor expression level. It is probably due to double nature of Sig1R action - in certain conditions it could act pro- or antiapoptotic. This action might depend on Sig1R activity resulting from its expression level.

摘要

非阿片类西格玛1受体(Sig1R)影响众多代谢功能,包括离子通道调节、应激反应和对生长信号的响应。由于这种影响,西格玛1受体配体对肿瘤细胞具有抗增殖和细胞毒性作用。此外,在某些类型的肿瘤中观察到其水平升高。结直肠癌是全球最常见的癌症之一,其临床进展已有详细描述。本研究的目的是评估人结直肠癌及结直肠癌肝转移在肿瘤发展不同阶段中西格玛1受体mRNA的表达水平。从30例患者中分离出mRNA:18例患有结直肠癌(CRC),12例患有结直肠癌肝转移(CRCLM)。使用特异性引物通过聚合酶链反应扩增Sig1R基因的cDNA。通过测量光密度确定Sig1R mRNA的表达水平。CRC和CRCLM中Sig1R的表达水平升高。在国际抗癌联盟(UICC)III期观察到Sig1R mRNA的最高水平。我们还显示UICC分期和肿瘤定位与Sig1R表达水平之间存在显著相互作用。UICC分期与患者年龄之间没有相互作用,尽管我们观察到老年患者中Sig1R mRNA水平显著降低。临床进展阶段、肿瘤定位和患者年龄似乎是影响西格玛1受体表达水平的重要因素。这可能是由于Sig1R作用的双重性质——在某些情况下它可能具有促凋亡或抗凋亡作用。这种作用可能取决于其表达水平所产生的Sig1R活性。

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