Most tumors in transgenic mice with human c-Ha-ras gene contained somatically activated transgenes - PubMed (original) (raw)
. 1990 Aug;5(8):1195-200.
Affiliations
- PMID: 2202951
Most tumors in transgenic mice with human c-Ha-ras gene contained somatically activated transgenes
A Saitoh et al. Oncogene. 1990 Aug.
Abstract
Two independent transgenic mouse lines carrying human hybrid c-Ha-ras genes with their own promoter region encoding prototype products, were established. In these lines, about 50% of transgenic offspring had tumors within 18 months. The tumors developed in restricted tissues and about 60% of affected mice had angiosarcomas. The transgenes were expressed both in the tumors and in all normal tissues. However, somatic mutational activation was detected only in the transgenes of the tumors. The point mutation at the 61st codon, from CAG(Gln) to CTG(Leu), was detected in all angiosarcomas (22/22), some lung adenocarcinomas (3/11) and Harderian gland adenocarcinomas (4/7) in both lines. The other point mutation at the 12th codon from GGC(Gly) to GTC(Val) was detected in two of the four skin papillomas. No mutations on these codons were detected in normal tissues of transgenic mice. Nontransgenic littermates had no tumors at all. From these results, it was strongly suggested that the mouse tumors do not develop only by the expression of the transgenes, and that definite somatic point mutation of the human c-Ha-ras transgenes in certain cell types may be a causative event in tumorigenesis in these transgenic mice.
Similar articles
- Chemically induced tumors in transgenic mice carrying prototype human c-Ha-ras genes.
Katsuki M, Ando K, Saitoh A, Doi S, Kimura M, Takahashi R, Hasegawa T, Yokoyama M, Nomura T, Izawa M, et al. Katsuki M, et al. Princess Takamatsu Symp. 1991;22:249-57. Princess Takamatsu Symp. 1991. PMID: 1844246 Review. - Chemically induced forestomach papillomas in transgenic mice carry mutant human c-Ha-ras transgenes.
Ando K, Saitoh A, Hino O, Takahashi R, Kimura M, Katsuki M. Ando K, et al. Cancer Res. 1992 Feb 15;52(4):978-82. Cancer Res. 1992. PMID: 1737360 - Embryonal tumors from transgenic mouse zygotes carrying human activated c-Ha-ras genes.
Katsuki M, Kimura M, Hata J, Takahashi R, Nozawa S, Yokoyama M, Izawa M, Sekiya T, Nishimura S, Nomura T. Katsuki M, et al. Mol Biol Med. 1989 Dec;6(6):567-72. Mol Biol Med. 1989. PMID: 2483936 - Transgenic rats carrying copies of the human c-Ha-ras proto-oncogene exhibit enhanced susceptibility to N-butyl-N-(4-hydroxybutyl)nitrosamine bladder carcinogenesis.
Ota T, Asamoto M, Toriyama-Baba H, Yamamoto F, Matsuoka Y, Ochiya T, Sekiya T, Terada M, Akaza H, Tsuda H. Ota T, et al. Carcinogenesis. 2000 Jul;21(7):1391-6. Carcinogenesis. 2000. PMID: 10874018 - The rasH2 transgenic mouse: nature of the model and mechanistic studies on tumorigenesis.
Tamaoki N. Tamaoki N. Toxicol Pathol. 2001;29 Suppl:81-9. doi: 10.1080/019262301753178492. Toxicol Pathol. 2001. PMID: 11695564 Review.
Cited by
- The complete Kaposi sarcoma-associated herpesvirus genome induces early-onset, metastatic angiosarcoma in transgenic mice.
Sin SH, Eason AB, Kim Y, Schneider JW, Damania B, Dittmer DP. Sin SH, et al. Cell Host Microbe. 2024 May 8;32(5):755-767.e4. doi: 10.1016/j.chom.2024.03.012. Epub 2024 Apr 22. Cell Host Microbe. 2024. PMID: 38653242 - Survey of tumorigenic sensitivity in 6-month rasH2-Tg mice studies compared with 2-year rodent assays.
Hisada S, Tsubota K, Inoue K, Yamada H, Ikeda T, Sistare FD. Hisada S, et al. J Toxicol Pathol. 2022 Jan;35(1):53-73. doi: 10.1293/tox.2021-0031. Epub 2021 Nov 1. J Toxicol Pathol. 2022. PMID: 35221496 Free PMC article. - rasH2 mouse: reproducibility and stability of carcinogenicity due to a standardized production and monitoring system.
Tsutsumi H, Inoue R, Yasuda M, Takahashi R, Suzuki M, Urano K. Tsutsumi H, et al. J Toxicol Pathol. 2022 Jan;35(1):19-24. doi: 10.1293/tox.2021-0068. Epub 2021 Nov 19. J Toxicol Pathol. 2022. PMID: 35221492 Free PMC article. Review. - Inhibitory Effects of Glucosylceramide on Tumorigenesis Induced by a Carcinogen in Mice.
Fujiwara K, Yazama H, Donishi R, Koyama S, Fukuhara T, Takeuchi H. Fujiwara K, et al. Laryngoscope. 2020 Nov;130(11):E593-E597. doi: 10.1002/lary.28449. Epub 2019 Dec 6. Laryngoscope. 2020. PMID: 31808958 Free PMC article. - From Classical Toxicology to Tox21: Some Critical Conceptual and Technological Advances in the Molecular Understanding of the Toxic Response Beginning From the Last Quarter of the 20th Century.
Choudhuri S, Patton GW, Chanderbhan RF, Mattia A, Klaassen CD. Choudhuri S, et al. Toxicol Sci. 2018 Jan 1;161(1):5-22. doi: 10.1093/toxsci/kfx186. Toxicol Sci. 2018. PMID: 28973688 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Molecular Biology Databases
Research Materials