TY - JOUR
T1 - Increased expression of cytoplasmic HuR in familial adenomatous polyposis
AU - Brosens, Lodewijk A.A.
AU - Keller, Josbert J.
AU - Pohjola, Leena
AU - Haglund, Caj
AU - Morsink, Folkert H.
AU - Iacobuzio-Donahue, Christine
AU - Goggins, Michael
AU - Giardiello, Francis M.
AU - Ristimäki, Ari
AU - Offerhaus, G. Johan A.
N1 - Funding Information:
Supported by The Netherlands Digestive Disease Foundation (MLDS WS 04-06), The John G. Rangos, Sr. Charitable Foundation, The Clayton Fund, and NIH grants CA 53801, 63721, 51085, and P50 CA 93-16.
PY - 2008/3
Y1 - 2008/3
N2 - 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) Materials and 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.
AB - 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) Materials and 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.
KW - Adenoma-carcinoma sequence
KW - COX-2
KW - Colorectal cancer
KW - Familial adenomatous polyposis
KW - HuR
KW - Tumorigenesis
KW - mRNA stability
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U2 - 10.4161/cbt.7.3.5417
DO - 10.4161/cbt.7.3.5417
M3 - Article
C2 - 18094611
AN - SCOPUS:45349109202
SN - 1538-4047
VL - 7
SP - 424
EP - 427
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 3
ER -