Expression of the ELAV-like protein HuR is associated with higher tumor grade and increased cyclooxygenase-2 expression in human breast carcinoma.
OBJECTIVE
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.


METHODS
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.
Institute of Pathology, Charité Hospital, Berlin, Germany. carsten.denkert@charite.de
Carsten
C
Denkert
Wilko
W
Weichert
Klaus-Jürgen
KJ
Winzer
Berit-Maria
BM
Müller
Aurelia
A
Noske
Silvia
S
Niesporek
Glen
G
Kristiansen
Hans
H
Guski
Manfred
M
Dietel
Steffen
S
Hauptmann
D000704:Analysis of Variance; D000954:Antigens, Surface / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D044584:Carcinoma, Ductal / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D051546:Cyclooxygenase 2; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases