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Publication : High frequency of mammary adenocarcinomas in metallothionein promoter-human growth hormone transgenic mice created from two different strains of mice.

First Author  Törnell J Year  1992
Journal  J Steroid Biochem Mol Biol Volume  43
Issue  1-3 Pages  237-42
PubMed ID  1525063 Mgi Jnum  J:72119
Mgi Id  MGI:2151749 Doi  10.1016/0960-0760(92)90213-3
Citation  Tornell J, et al. (1992) High frequency of mammary adenocarcinomas in metallothionein promoter-human growth hormone transgenic mice created from two different strains of mice. J Steroid Biochem Mol Biol 43(1-3):237-42
abstractText  Transgenic mice were developed by injecting a mouse metallothionein promoter-human growth hormone (Mt-hGH) gene fragment into the pronucleus of C57Bl x DBA/2J-f2 or C57Bl x CBA-f2 one cell embryos. Six founder animals with the C57Bl x DBA genetic background grew 1.3-2.2 times larger than littermate controls and had higher levels of hGH in plasma (4.6-279 mU/l). Three of the four female transgenic founders developed malignant papillar adenocarcinomas of mammary origin at 27-43 weeks of age. One male transgenic founder was successfully mated and two of three female transgenic offsprings developed mammary tumors. To examine if the tumor induction was dependent on the strain of mice used the experiments were repeated using animals with different genetic background. Fourteen female hGH transgenic mice from five founder animals were generated using C57Bl x CBA-f2 mice. Thirteen of the animals had elevated levels of hGH in plasma (7-1960 mU/l) and grew larger than control animals. Nine of the animals developed mammary adenocarcinomas. Four of the hGH expressing animals did not demonstrate macroscopic tumor formation but have not yet been analyzed histologically. The present study suggests that markedly elevated endogenous levels of GH cause mammary carcinoma in hGH transgenic mice. The present animal model might prove useful for studying molecular mechanisms involved in the development of hormonally induced mammary tumors.
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