Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2
Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2
复制标题
DOI：
10.1038/modpathol.3800645
复制
发表时间：
2006-09-01
期刊：
影响因子：
7.5
通讯作者：
Weichert, Wilko
中科院分区：
文献类型：
--
作者：
Denkert, Carsten;Koch, Ines;Weichert, Wilko
有越来越多的证据表明，翻译后事件的贡献-除了遗传变化-恶性肿瘤的进展。这些翻译后改变可能为新的治疗方法提供靶点。ELAV样蛋白HuR稳定一组在其非翻译区含有富含AU的元件的细胞mRNA。为了研究翻译后改变对结肠癌进展和考克斯-2过表达的可能贡献，我们研究了一组结肠直肠腺癌和结肠癌细胞系中HuR和考克斯-2的表达。所有细胞系均显示HuR mRNA和蛋白的表达。在结肠癌的肿瘤组织中，我们观察到两种不同的染色模式的HuR：在98%的情况下，以及在53%的情况下，一个额外的细胞质表达的核表达。考克斯-2在63%的乳腺癌中表达。HuR的胞浆表达与考克斯-2表达的增加以及肿瘤的高分期显著相关。在单因素Kaplan-Meier分析中，分级、肿瘤分期和淋巴结状态而不是HuR或考克斯-2表达是总生存期的预后因素。我们的研究结果表明，HuR在结肠癌中的过度表达可能是控制环氧化酶-2的mRNA稳定性的调节途径的一部分，并为mRNA稳定性失调对结肠直肠癌进展的贡献提供了一个有趣的例子。基于我们的研究结果，进一步的研究是必要的，以调查是否HuR可能是一个潜在的目标，为分子肿瘤治疗。
There is growing body of evidence that post-translational events contribute-in addition to genetic changes-to the progression of malignant tumors. These post-translational alterations may provide targets for new therapeutic approaches. The ELAV-like protein HuR stabilizes a group of cellular mRNAs which contain AU-rich elements in their 30 untranslated region. To investigate a possible contribution of post-translational changes to the progression of colon cancer and to overexpression of COX-2, we studied expression of HuR and COX-2 a cohort of colorectal adenocarcinomas and in colon cancer cell lines. All cell lines showed an expression of HuR mRNA and protein. In tumor tissue of colon carcinomas we observed two different staining patterns of HuR: A nuclear expression in 98% as well as an additional cytoplasmic expression in 53% of cases. COX-2 was expressed in 63% of carcinomas. Cytoplasmic expression of HuR was significantly associated with increased COX-2 expression as well as with high tumor stage. In univariate Kaplan-Meier analysis, grading, tumor stage and nodal status but not HuR or COX-2 expression were prognostic factors for overall survival. Our results suggest that the overexpression of HuR in colon cancer may be part of a regulatory pathway that controls the mRNA stability of cyclooxygenase-2 and provides an interesting example for a contribution of a dysregulation of mRNA stability to the progression of colorectal cancer. Based on our results, further studies are necessary to investigate whether HuR might be a potential target for a molecular tumor therapy.