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Carcinogenesis Advance Access published online on March 28, 2003
Carcinogenesis, doi:10.1093/carcin/bgg030
© 2003 by Oxford University Press
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© 2003 Oxford University Press

CANCER BIOLOGY

Global expression analysis of N-methyl-N'-nitro-N-nitrosoguanidine-induced rat stomach carcinomas using oligonucleotide microarrays

Masanobu Abe 1, Satoshi Yamashita 2, Takashi Kuramoto 2, Yoshikazu Hirayama 2, Tetsuya Tsukamoto 3, Tsutomu Ohta 4, Masae Tatematsu 3, Misao Ohki 4, Tsuyoshi Takato 5, Takashi Sugimura 2, Toshikazu Ushijima 2*

1 Carcinogenesis Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan; Department of Oral Surgery, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo 135-8655, Japan
2 Carcinogenesis Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan
3 Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa, Nagoya 464-8681, Japan
4 Center for Medical Genomics, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan
5 Department of Oral Surgery, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo 135-8655, Japan

* Corresponding author. E-mail: tushijim{at}gan2.res.ncc.go.jp.

Received 16 December 2002 ; revised 20 February 2003 ; accepted 21 February 2003

Abstract

Rat stomach carcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are widely used as a model for differentiated-type human stomach carcinomas. Here, we analyzed expression profiles in five MNNG-induced rat stomach carcinomas by the high-density oligonucleotide microarray containing approximately 8,000 probe sets. 244 and 208 genes were up- and down-regulated, respectively, by three fold and over in four or five carcinomas. Up-regulated genes included those involved in the extracellular matrix remodeling (ie: Collagen types I, III, V, MMP3), immune response (ie: lysozyme, complements), and in ossification (ie: Osteoblast-specific factor). Genes down-regulated included those related to hydrocarbon metabolism (ie: aldose A, aldehyde dehydrogenase), gastric juice (ion transporter genes) and mucous production (Mucin 5) and gastric hormones (gastrin and somatostatin). The expression profile of the MNNG-induced rat stomach carcinomas shared many features with human stomach carcinomas while cyclin D1 was down-regulated in rat stomach carcinomas but up-regulated in human stomach carcinomas. When the expression profile of the MNNG-induced rat stomach carcinomas was compared with those of two kinds of rat mammary carcinomas, only 13 genes were commonly altered. These results showed that MNNG-induced stomach carcinomas possessed infiltrating capacity and had lost differentiated phenotypes of the stomach, in the same way as human stomach carcinomas, and could be used as a good model for them from the viewpoint of molecular expression profile.

Microarray, Rat stomach carcinomas, MNNG, Expression profiles
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