A retroviral vector is being employed to place an activated oncogene directly into mammary gland duct cells of female rats. These activated oncogenes are be directly administered into the rat mammary epithelial cells employing a replication defective retrovirus. Employing this methodology one can induce tumors employing a number of different oncogenes e.g. Neu, Ha Ras. Focal ductal lesions are induced in rat mammary tissue employing a variety of oncogenes. Second the resulting tumors are being characterized for hormonal responsiveness. Interestingly approximately 45% of the HaRas induced tumors and approximately 15% of the Neu induced tumors are hormonally independent. Hormone independence was defined functionally by the fact that these tumors grew out despite ovariectomy of rats shortly after they are administered the virus vector containing Ras or Neu. These results are confirmed by the fact that a significant percentage of palpable lesions which arise following viral administration are similarly non responsive to ovariectomy. Furthermore the ability to administer various doses of the virus should allow one to innoculate a different viral load in rats which will be ovariectomized, or which will not be ovariectomized to obtain a similar number of tumors in either. Finally the non transgenic nature of this approach means that one can use this method for screening new agents. Finally the reproducible nature of development and size of the resulting lesions allows one to examine for potential modulable endpoints employing this system.
