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Difference in the Response of neu and ras Oncogene-induced Rat Mammary Carcinomas to Early and Late Ovariectomy¹

Department of Human Oncology and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin 53792

Rat mammary carcinomas were induced by directly inserting activated neu or ras genes into in situ rat mammary ductal cells using replication-defective retroviral vectors. neu was over 200 times more potent than ras in inducing rat mammary carcinomas. Ovariectomy 2 days postinfection dramatically reduced the occurrence of carcinomas induced by neu and extended their latency. In general, early ovariectomy had much less effect on the occurrence of carcinomas induced by ras and had no significant effect on their latency. Carcinomas induced by neu in ovariectomized rats had down-regulated estrogen receptor and progesterone receptor, while those induced by ras had only down-regulated progesterone receptor. Fully progressed mammary carcinomas in intact rats induced by both neu and ras had a similar response to ovariectomy, with an approximate regression rate of 60%. These data suggest that the activation of ras, but not neu, can replace at least some functions performed by ovarian hormones in the early phases of mammary carcinogenesis. These data also suggest a role for antiestrogen drug therapy in the prevention of neu-associated breast cancer.

¹ Supported by USPHS NIH Grant CA44387.

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

Received 1/10/92. Accepted 5/15/92.

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