Expression of the ELAV-like protein HuR is associated with higher tumor grade and increased cyclooxygenase-2 expression in human breast carcinoma
Expression of the ELAV-like protein HuR is associated with higher tumor grade and increased cyclooxygenase-2 expression in human breast carcinoma
复制标题
DOI：
10.1158/1078-0432.ccr-04-0070
复制
发表时间：
2004-08-15
影响因子：
11.5
通讯作者：
Hauptmann, S
中科院分区：
文献类型：
--
作者：
Denkert, C;Weichert, W;Hauptmann, S
目的：人类ELAV（胚胎致死异常视觉）样蛋白HuR稳定了一组在其3 '非翻译区含有富含AU元件的细胞mRNA。细胞培养研究表明，环氧化酶（考克斯）-2的mRNA可以通过HuR.Experimental Design来稳定。为了研究mRNA稳定性失调对癌症进展和考克斯-2过度表达的可能贡献，我们通过免疫组织化学研究了HuR在208例原发性乳腺癌中的表达。在61%的病例中观察到细胞核表达;在30%的病例中观察到另外的细胞质表达。HuR的表达与考克斯-2表达的增加显著相关;这种相关性在胞浆HuR表达中尤其显著（P < 0.0005）。我们进一步观察到细胞质（P = 0.002）或细胞核HuR（P = 0.027）表达与肿瘤分级增加显著相关。只有13%的1级癌细胞胞浆表达HuR，而3级癌细胞胞浆表达HuR的比例为46%。HuR的表达和其他临床病理参数，如组织学类型，肿瘤大小，或淋巴结状态以及患者survival.Conclusions：我们的研究结果表明，HuR在肿瘤组织中的过度表达可能是一个调节途径的一部分，控制的mRNA稳定性的几个重要目标，在肿瘤生物学，如考克斯-2。基于我们的研究结果，有必要进一步研究HuR是否可能成为分子肿瘤治疗的潜在靶点。
Purpose: The human ELAV (embryonic lethal abnormal vision)-like protein HuR stabilizes a certain group of cellular mRNAs that contain AU-rich elements in their 3'-untranslated region. Cell culture studies have shown that the mRNA of cyclooxygenase (COX)-2 can be stabilized by HuR.Experimental Design: To investigate a possible contribution of dysregulation of mRNA stability to the progression of cancer and to overexpression of COX-2, we studied expression of HuR in 208 primary breast carcinomas by immunohistochemistry.Results: There were two different staining patterns of HuR in tumor tissue of breast carcinomas: nuclear expression was seen in 61 % of cases; and an additional cytoplasmic expression was seen in 30 % of cases. Expression of HuR was significantly associated with increased COX-2 expression; this association was particularly significant for cytoplasmic HuR expression (P < 0.0005). We further observed a significant association of cytoplasmic (P = 0.002) or nuclear HuR (P = 0.027) expression with increased tumor grade. Only 13% of the grade 1 carcinomas showed cytoplasmic expression of HuR, compared with 46% of the grade 3 carcinomas. There was no significant correlation between HuR expression and other clinicopathological parameters such as histological type, tumor size, or nodal status as well as patient survival.Conclusions: Our results suggest that overexpression of HuR in tumor tissue may be part of a regulatory pathway that controls the mRNA stability of several important targets in tumor biology, such as COX-2. Based on our results, additional studies are necessary to investigate whether HuR might be a potential target for molecular tumor therapy.