J Vet Sci.  2000 Dec;1(2):121-126.

Overexpression of cyclin D1 and cyclin E in 1,2-dimethylhydrazine dihydrochloride-induced rat colon carcinogenesis

• Hur K
• Kim JR
• Yoon BI
• Lee JK
• Choi JH
• Oh GT
• Kim DY

Abstract

Deregulation of G1 cyclins has been reported in several human and rodent tumors including colon cancer. To investigate the expression pattern of G1 cyclins in 1,2- dimethyl-hydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis, we studied the expression of cyclin D1 and cyclin E by quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry (IHC). The mRNA level of cyclin D1 was increased 1.2-fold in adenocarcinomas but not significantly in adenomas, when compared with normal rat colonic mucosa (p<0.05). The cyclin E mRNA level was increased 2.7-fold in adenomas and 3.3-fold in adenocarcinomas (p<0.05). The PCNA mRNA level was also increased 1.9-fold in adenomas and 1.8-fold in adenocarcinomas (p<0.05). Immunohistochemical staining revealed exclusive nuclear staining of the neoplastic cells for cyclin D1, cyclin E and PCNA. Cyclin D1 expression was detected in 56.3% of the adenomas and in 61.5% of the adenocarcinomas examined, whereas cyclin E expression was detected in 87.5% of the adenomas and in 92.3% of the adenocarcinomas. Overall, cyclin D1, cyclin E and PCNA expression was significantly increased at both the mRNA and protein levels in normal colonic mucosa, adenomas and adenocarcinomas, but there was no significant difference in the degree of expression of these genes in adenomas and adenocarcinomas. Our results indicate that the overexpression of cyclin D1 and cyclin E may play an important role during the multistage process of rat colon carcinogenesis, at a relatively early stage, and may disturb cell-cycle control in benign adenomas, and thereafter, participate in tumor progression.

Keyword

cell cycle; cyclin D1; cyclin E; colon cancer

MeSH Terms

1,2-Dimethylhydrazine/toxicity
Adenocarcinoma/*chemically induced/metabolism
Adenoma/*chemically induced/metabolism
Animals
Carcinogens/toxicity
Cell Cycle/drug effects/physiology
Colon/metabolism
Colonic Neoplasms/*chemically induced/metabolism
Cyclin D1/*biosynthesis/genetics
Cyclin E/*biosynthesis/genetics
Gene Expression Regulation, Neoplastic
Immunohistochemistry
Male
Proliferating Cell Nuclear Antigen/biosynthesis/genetics
RNA, Messenger/metabolism
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction