The possible mechanism of enhanced carcinogenesis induced by genotoxic carcinogens in rasH2 mice.
Microarray and RT-PCR analyses were performed for the transgene and Ras-related genes in forestomach squamous cell carcinomas (SCCs) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in rasH2 mice; these results were compared with our previous molecular data of N-ethyl-N-nitrosourea-induced forestomach SCCs and urethane-induced lung adenomas in rasH2 mice. Overexpression of the transgene was detected in the DMBA-induced SCCs, suggesting that the transgene plays an important role in enhanced carcinogenesis in rasH2 mice. In addition, the mouse endogenous ras genes were up-regulated in the DMBA-induced SCCs, and are probably involved in the tumorigenesis of forestomach SCCs. Genes such as osteopontin, Cks1b, Tpm1, Reck, gelsolin, and amphiregulin that were commonly altered in these three different carcinogen-induced tumors may contribute to the development of tumors in rasH2 mice.
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu City, Tokyo 183-8509, Japan. mokamura@cc.tuat.ac.jp
Miwa
M
Okamura
Akira
A
Unami
Mitsuyoshi
M
Moto
Masako
M
Muguruma
Tadashi
T
Ito
Meilan
M
Jin
Yuji
Y
Oishi
Yoko
Y
Kashida
Kunitoshi
K
Mitsumori
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene