Increased expression of cytoplasmic HuR in familial adenomatous polyposis.
BACKGROUND
HuR is an mRNA stability factor that binds to the AU-rich element-containing 3' untranslated region of the transcript. HuR overexpression is associated with increased tumor growth. Increased cytoplasmic HuR expression occurs in several cancer types, including colorectal cancer where it may contribute to the increased cyclooxygenase-2 (COX- 2) expression observed during tumorigenesis. To investigate expression of HuR in the colorectal adenoma-carcinoma sequence, we examined expression of HuR in colorectal mucosa of patients with familial adenomatous polyposis (FAP) and sporadic colorectal cancer with correlation to COX-2 expression.


RESULTS
Cytoplasmic HuR staining was found in the epithelium of 10% of normal mucosa, 14.3% of adenomas and 88.9% of adenocarcinomas from FAP patients (p < 0.01) and in 68.8% of sporadic colorectal carcinomas. High epithelial COX-2 immunostaining was observed in 10% of normal, 8% of adenomas and all adenocarcinomas from FAP patients (p < 0.01) and in 69.5% of sporadic colorectal carcinomas. Positive cytoplasmic HuR immunostaining correlated with high COX-2 immunoreactivity in colon mucosa of FAP patients (p < 0.01) and in sporadic colorectal carcinomas. (p = 0.016)


METHODS
HuR and COX-2 protein expression were studied by immunohistochemistry of normal colon mucosa (N=20), adenomas (N=112), carcinomas (N=9) from patients with FAP, and 141 sporadic colorectal adenocarcinomas (Dukes B and C).


CONCLUSIONS
HuR is increasingly expressed in the cytoplasmic epithelial compartment in consecutive stages of the adenoma-carcinoma sequence in FAP. Also, COX-2 levels correlate with cytoplasmic expression of HuR in colonic epithelium of FAP patients and in sporadic colorectal cancer specimens. The role of cytoplasmic expression of HuR as a biomarker for progression of adenomas in FAP needs further study.
Brosens
Lodewijk A A
LA
Department of Pathology, University Medical Center, Utrecht, the Netherlands. l.a.a.brosens@umcutrecht.nl
Keller
Josbert J
JJ
Pohjola
Leena
L
Haglund
Caj
C
Morsink
Folkert H
FH
Iacobuzio-Donahue
Christine
C
Goggins
Michael
M
Giardiello
Francis M
FM
Ristimäki
Ari
A
Offerhaus
G Johan A
GJ
D011125:Adenomatous Polyposis Coli / Q000201:enzymology / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics*; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D003593:Cytoplasm / Q000502:physiology; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human