One of the approaches that has been used to identify genes involved in the multi-step process of carcinogenesis has been the cloning of common integration sites of naturally occurring oncogenic retroviruses. These retroviruses can induce tumors by inserting themselves close to or within genes that are involved in tumorigenesis. This proposal will use retroviral induced mutagenesis in a novel manner to identify genes that are involved in the progression of breast cancer. Mammary cell lines that are non- tumorigenic in nude mice will be infected with a defective retrovirus. Since retroviral insertion is random, it is expected that the insertion of the retrovirus will activate or inactivate genes that are important in tumor progression. These cells will then be capable of generating tumors and, in certain cases, metastases when injected into nude mice. The cloning of common integration sites present in the DNA extracted from cell lines derived from these tumors and metastases will allow the identification of genes involved in the generation and progression of the malignant phenotype.
