Expression of HuR is associated with increased cyclooxygenase-2 expression in uterine cervical carcinoma
Expression of HuR is associated with increased cyclooxygenase-2 expression in uterine cervical carcinoma
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DOI：
10.1097/01.pgp.0000236946.82334.07
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发表时间：
2007-07-01
影响因子：
2.4
通讯作者：
Lee, Chul-Min
中科院分区：
文献类型：
--
作者：
Lim, Sung-Jig;Kim, Hyun Jung;Lee, Chul-Min
人类胚胎致死性异常视觉样蛋白 Hu 抗原 R (HuR) 是一种信使 RNA (mRNA) 结合蛋白，可稳定某些细胞 mRNA，这些 mRNA 的 3-非翻译区含有富含腺苷酸/尿苷酸的元件。 HuR主要位于细胞核中，但它在细胞核和细胞质之间穿梭。在细胞质中，它可以稳定某些转录本。据报道，HuR 可稳定乳腺癌、卵巢癌、结肠癌、胃癌、肺癌和脑癌中的环氧合酶-2 (COX-2) mRNA。我们使用免疫组织化学方法研究了 308 个原发性宫颈癌中 HuR 和 COX-2 的表达。 280例（90.9%）细胞核表达HuR，61例（19.8%）细胞质HuR表达。核HuR的表达与分期显着相关（P = 0.031）。我们发现 135 名患者（43.8%）的 COX-2 蛋白呈阳性反应。 COX-2阳性病例中，核HuR表达较高，但差异无统计学意义。细胞质 HuR 表达与肿瘤大小 (P = 0.029)、分期 (P = 0.005) 和淋巴/血管侵犯 (P < 0.001) 显着相关。仅考虑鳞状细胞病变（原位癌、微浸润性鳞状细胞癌[SCC]和浸润性SCC），与微浸润性鳞状细胞癌或原位癌相比，浸润性鳞状细胞癌中HuR的细胞质表达显着增加（P = 0.005）。细胞质 HuR 表达与 COX-2 相关 (P < 0.001)。 HuR（核或细胞质）表达与患者生存率之间没有显着相关性。我们的结果表明，HuR 的细胞质过度表达与具有侵袭性临床病理特征的宫颈癌相关，并且 HuR 可能有助于某些宫颈癌中 COX-2 mRNA 的稳定。
The human family embryonic-lethal abnormal vision-like protein Hu antigen R (HuR) serves as a messenger RNA (mRNA)-binding protein and stabilizes a certain group of cellular mRNAs that contain adenylate/uridylate-rich elements in their 3-untranslated region. The HuR is predominantly located in the nucleus, but it shuttles between the nucleus and the cytoplasm. In the cytoplasm, it can stabilize certain transcripts. Reportedly, the mRNA of cyclooxygenase-2 (COX-2) can be stabilized by HuR in breast, ovary, colon, stomach, lung, and brain cancers. We investigated the expression of HuR and COX-2 in 308 primary uterine cervical carcinomas using immunohistochemistry. Nuclear HuR expression was seen in 280 (90.9%) of the cases, and cytoplasmic HuR expression was observed in 61 (19.8%) of the cases. The expression of nuclear HuR was significantly associated with stage (P = 0.031). We found that 135 patients (43.8%) showed positive reaction for the COX-2 protein. In the COX-2 positive cases, nuclear HuR expression was higher, but the difference was not statistically significant. Cytoplasmic HuR expression was significantly associated with tumor size (P = 0.029), stage (P = 0.005), and lymphatic/vascular invasion (P < 0.001). Considering only squamous cell lesions (carcinoma in situ, microinvasive squamous cell carcinoma [SCC], and invasive SCC), the cytoplasmic expression of HuR significantly increased in invasive SCC compared with microinvasive SCC or carcinoma in situ (P = 0.005). Cytoplasm HuR expression correlated with COX-2 (P < 0.001). There was no significant correlation between HuR (nuclear or cytoptasmic) expression and patient survival. Our results suggest that the cytoplasmic overexpression of HuR is associated with uterine cervical carcinomas with aggressive clinicopathologic features and that HuR might contribute to the stabilization of COX-2 mRNA in some uterine cervical carcinomas.