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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

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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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References

    1. ) Sukumar , S. , McKenzie , K. and Chen , Y.Animal models for breast cancer . Mutat. Res. , 333 , 37 – 44 ( 1995. ). - PubMed
    1. ) Arafah , B. M. , Gullino , P. M. , Manni , A. and Pearson , O. H.Effect of ovariectomy on hormone receptors and growth of N‐nitrosomethylurea‐induced mammary tumors in the rat . Cancer Res. , 40 , 4628 – 4630 ( 1980. ). - PubMed
    1. ) Sukumar , S. , Carney , W. P. and Barbacid , M.Independent molecular pathways in initiation and loss of hormone responsiveness of breast carcinomas . Science , 240 , 524 – 526 ( 1988. ). - PubMed
    1. ) Williams , J. C. , Gusterson , B. , Humphreys , J. , Monaghan , P. , Coombes , R. C. , Rudland , P. and Neville , A. M.N‐ Methyl‐N‐nitrosourea‐induced rat mammary tumors. Hormone responsiveness but lack of spontaneous metastasis . J. Natl. Cancer Inst. , 66 , 147 – 155 ( 1981. ). - PubMed
    1. ) Kumar , R. , Sukumar , S. and Barbacid , M.Activation of ras oncogenes preceding the onset of neoplasia . Science , 248 , 1101 – 1104 ( 1990. ). - PubMed

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