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Frequent Induction of Mammary Carcinomas following neu Oncogene Transfer into in Situ Mammary Epithelial Cells of Susceptible and Resistant Rat Strains¹

Department of Human Oncology [W. S. K., J. Y. B., M. J. L., M. N. G.] and Environmental Toxicology Center [B. W., M. N. G.], University of Wisconsin-Madison, Madison, Wisconsin, 53792

Varying results have been reported on the role of neu oncogene in mammary carcinogenesis. In order to further address this issue, the activated neu oncogene was introduced into mammary epithelial cells in situ of both mammary carcinoma-susceptible Wistar Furth and resistant Copenhagen rats by infusing replication-defective recombinant retroviruses carrying the neu oncogene into the mammary gland lumen. At the highest virus titer tested, very high numbers of mammary carcinomas developed within 2 weeks in all exposed glands in both rat strains. When the virus titer was reduced, however, individual tumors occurred with varying latencies. In addition, not all of the neu-infected mammary cells progressed to form mammary carcinomas. These results suggest that while neu is a potent mammary transforming gene, either other events in addition to neu expression may be required for full malignant transformation or not all mammary ductal epithelial cells are able to be neoplastically transformed.

¹ Supported by Grants CA44387 and CA28954 from the USPHS, NIH.

² To whom requests for reprints should be addressed, at K4/332, UWCCC, Department of Human Oncology, 600 Highland Avenue, Madison, WI 53792.

Received 5/17/91. Accepted 8/ 7/91.

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