Mammary Carcinomas Induced in Human c-Ha-ras Proto-oncogene Transgenic Rats Are Estrogen-independent, but Responsive to d-Limonene Treatment.
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Accession number;02A0169404
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| Title;Mammary Carcinomas Induced in Human c-Ha-ras Proto-oncogene Transgenic Rats Are Estrogen-independent, but Responsive to d-Limonene Treatment. |
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Journal Title;Jpn J Cancer Res
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Journal Code:F0633A
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ISSN:0910-5050
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VOL.93;NO.1;PAGE.32-35(2002)
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| Figure&Table&Reference;FIG.1, TBL.2, REF.21 |
| Pub. Country;Japan |
| Language;English |
| 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. (author abst.) |
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