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Expression of the ELAV-Like Protein HuR Is Associated with Higher Tumor Grade and Increased Cyclooxygenase-2 Expression in Human Breast Carcinoma

2004; American Association for Cancer Research; Volume: 10; Issue: 16 Linguagem: Inglês

10.1158/1078-0432.ccr-04-0070

1557-3265

Carsten Denkert, Wilko Weichert, Klaus‐Jürgen Winzer, B. Müller, Aurelia Noske, Silvia Niesporek, Glen Kristiansen, Hans Guski, Manfred Dietel, Steffen Hauptmann,

RNA and protein synthesis mechanisms

Abstract 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.