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. 2002 Jan;93(1):32-5.
doi: 10.1111/j.1349-7006.2002.tb01197.x.

Mammary carcinomas induced in human c-Ha-ras proto-oncogene transgenic rats are estrogen-independent, but responsive to d-limonene treatment

Makoto Asamoto  1 , Tomonori Ota, Hiroyasu Toriyama-Baba, Naomi Hokaiwado, Akihiro Naito, Hiroyuki Tsuda
Affiliations

Mammary carcinomas induced in human c-Ha-ras proto-oncogene transgenic rats are estrogen-independent, but responsive to d-limonene treatment

Makoto Asamoto et al. Jpn J Cancer Res. 2002 Jan.

Abstract

We have previously shown that transgenic rats carrying three copies of the human c-Ha-ras proto-oncogene (Hras128) are highly susceptible to N-methyl-N-nitrosourea (MNU) mammary carcinogenesis. All transgenic rats treated with 50 mg / kg MNU, i.v. at 50 days of age, were found to rapidly develop multiple, large mammary carcinomas within as short a period as 8 weeks. In the present study, the effects of ovariectomy and treatment with d-limonene, known to inhibit mammary carcinogenesis in non-transgenic female rats, were investigated in Hras128 animals treated with MNU to clarify the role of the human c-Ha-ras proto-oncogene and to characterize the induced mammary carcinomas. Although ovariectomy completely inhibited development of mammary carcinomas in their wild-type counterparts, it did not affect either the incidence or the multiplicity of the mammary carcinomas in the Hras128 rats. On the other hand, treatment with d-limonene, an inhibitor of ras protein isoprenylation, inhibited the breast tumor development. These results indicate that aberrant c-Ha-ras gene expression is involved in ovarian hormone-independent growth and c-Ha-ras protein isoprenylation plays an important role in mammary carcinogenesis.

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