Expression of the cyclin D1 gene in rat colorectal aberrant crypt foci andtumors induced by azoxymethane

Cyclin D1 is a cell cycle regulator which is overexpressed in a variety of human cancers. We examined overexpression of cyclin D1 in several stages of rat colorectal carcinogenesis induced by azoxymethane (AOM) treatment. The level of cyclin D1 in 13 aberrant crypt foci (ACF) (atypical hyperplasias) , 22 colorectal tumors (14 non-invasive adenocarcinomas and eight invasive adenocarcinomas) was assessed by immunostaining using a polyclonal antibody . Cell proliferation of these samples was investigated by measurement of 5- bromo-2'-deoxyuridine-labeling index. Indices of cyclin D1-positive cells i n adenocarcinomas and atypical hyperplasias were significantly higher than that in normal crypts (P < 0.05). Moreover, cyclin D1-positive rates in the two types of adenocarcinomas were significantly higher than that in atypic al hyperplasias (P < 0.05). Staining of nuclear cyclin D1 was very strong i n almost all adenocarcinomas and four ACF. Comparisons of BrdU-positive ind ices in colorectal lesions showed similar results to the cyclin D1-positive indices. These results suggested that overexpession of cyclin D1 occurs ea rly in the multistep carcinogenesis, and plays an important role in rat col orectal carcinogenesis. (C) 1999 Elsevier Science Ireland Ltd. All rights r eserved.