Global expression analysis of N-methyl-N'-nitro-N-nitrosoguanidine-induced rat stomach carcinomas using oligonucleotide microarrays.
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 8000 probe sets. 244 and 208 genes were up- and down-regulated, respectively, by 3-fold and over in four or five carcinomas. Up-regulated genes included those involved in the extracellular matrix remodeling (i.e. Collagen types I, III, V, MMP3), immune response (i.e. lysozyme, complements) and in ossification (i.e. Osteoblast-specific factor). Genes down-regulated included those related to hydrocarbon metabolism (i.e. 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.
Abe
Masanobu
M
Carcinogenesis Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
Yamashita
Satoshi
S
Kuramoto
Takashi
T
Hirayama
Yoshikazu
Y
Tsukamoto
Tetsuya
T
Ohta
Tsutomu
T
Tatematsu
Masae
M
Ohki
Misao
M
Takato
Tsuyoshi
T
Sugimura
Takashi
T
Ushijima
Toshikazu
T
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D020224:Expressed Sequence Tags; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011912:Rats, Inbred ACI; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000235:genetics*
D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D008769:Methylnitronitrosoguanidine