Etiology-specific gene expression profiles in rat mammary carcinomas.
Identification of etiology of human cancers is important for effective cancer prevention, and attempts to estimate the roles of a variety of environmental carcinogens in human cancers are being made. Here, we applied cDNA microarray technology to estimate whether gene expression profiles of cancers would reflect their etiology. Using rat mammary carcinoma models, expression profiles were analyzed in two groups of carcinomas induced by distinct carcinogens but with the same histological classification. Four carcinomas induced by 7,12-dimethylbenz[a]anthracene (DMBA) and three carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and a high-fat diet were analyzed by a GeneChip oligonucleotide microarray that contained approximately 8000 rat genes. By hierarchical clustering analysis, the seven carcinomas were classified into two groups that exactly coincided with the DMBA-induced and the PhIP-induced groups. The correlation coefficient between the two groups was 0.63, and those between any carcinomas within each group ranged from 0.78 to 0.95. In addition, characteristic clusters of genes were also identified that highlighted distinct and common characteristics of both groups. Seventeen genes were down-regulated in the DMBA and up-regulated in the PhIP-induced groups. Thirty-three genes were regulated in the opposite manner. Our results indicated that gene expression profiles in cancers reflect their etiology and suggested a possibility that etiology of cancers could be retrospectively estimated from their expression profiles.
Kuramoto
Takashi
T
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Morimura
Keiichirou
K
Yamashita
Satoshi
S
Okochi
Eriko
E
Watanabe
Naoko
N
Ohta
Tsutomu
T
Ohki
Misao
M
Fukushima
Shoji
S
Sugimura
Takashi
T
Ushijima
Toshikazu
T
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007093:Imidazoles / Q000633:toxicity*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D007093:Imidazoles; D015127:9,10-Dimethyl-1,2-benzanthracene; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine