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Differential expression of cyclo‐oxygenase‐2 and nuclear β‐catenin in colorectal cancer tissue
Author(s) -
TATSUGUCHI A.,
KISHIDA T.,
FUJIMORI S.,
TANAKA S.,
GUDIS K.,
SHINJI S.,
FURUKAWA K.,
TAJIRI T.,
SUGISAKI Y.,
FUKUDA Y.,
SAKAMOTO C.
Publication year - 2006
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2006.00039.x
Subject(s) - cyclin d1 , colorectal cancer , catenin , adenomatous polyposis coli , cancer research , carcinogenesis , medicine , immunohistochemistry , mouse model of colorectal and intestinal cancer , familial adenomatous polyposis , cancer , pathology , biology , wnt signaling pathway , cell cycle , gene , genetics
Summary Background Both adenomatous polyposis coli ( APC ) gene mutation and cyclo‐oxygenase (COX)‐2 are thought to play key roles in colorectal carcinogenesis. Nuclear accumulation of β ‐catenin results from APC gene mutation, which leads to enhanced transcription and activation of target genes, including cyclin D1. In vitro studies suggest that Cox‐2 transcription is directly regulated by β ‐catenin/TCF complexes. Aim To investigate the relationship between cellular localization of β ‐catenin and COX‐2 in colorectal cancer. Methods We performed immunohistochemical analysis of β ‐catenin, cyclin D1 and COX‐2 expression in 50 resected colorectal cancer cases. Results The proportion of cases positive for cyclin D1 was higher in nuclear β ‐catenin‐positive cases than in negative cases ( P < 0.001). Serial sections revealed that the co‐localization of cyclin D1 and nuclear β ‐catenin was most frequently evident in the tumour cells at the advancing margin of invasive carcinoma. Conversely, there was no association between COX‐2 and nuclear β ‐catenin expression, either topographically or statistically. The staining patterns for COX‐2 and nuclear β ‐catenin differed; COX‐2 was diffuse and homogeneous, whereas nuclear β ‐catenin was focal and preferentially distributed at the invasive margin of cancer cells. Conclusions These two important modulators of colorectal tumourigenesis are differentially expressed. Cox‐2 and β ‐catenin transcription may be activated by different pathways.