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Defective Retrovirus Insertion Activates c-Ha-ras Proto-oncogene in an MNU-Induced Rat Mammary Carcinoma

https://doi.org/10.1006/bbrc.1998.9059Get rights and content

Abstract

Endogenous retrovirus sequences are present in the genome of a wide variety of animal species. The activation of the proto-oncogenes of the ras family, particularly c-Ha-ras, by either point mutation or overexpression, has been shown to be associated with a vast number of different cancers. Here we report that the insertion of a defective retrovirus in the −1 intron of rat c-Ha-ras is responsible for the activation of the gene by over 10-fold overexpression in an MNU-induced rat mammary cancer. A portion of the 3′ end of the retroviral sequence is expressed as a part of the c-Ha-ras transcript in the carcinoma tissue, indicating the direct involvement of this element in the transcription of the c-Ha-ras gene. The c-Ha-ras structural gene transcribed by the promoter of the defective retroviral element can neoplastically transform the NIH 3T3 cell line upon transfection.

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    C. Zarvos

    1

    To whom correspondence should be addressed at present address: Laboratory of Molecular Biology, Building 37 Room 4B20, National Cancer Institute, NIH, Bethesda, MD 20892. Fax: (301) 402-1344. E-mail:[email protected].

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