Methods to study primary tumor cells and residual tumor cells in mouse models of oncogene dependence.

The studies of oncogene dependence are aimed to understand an unfortunate and puzzling aspect of targeted anticancer treatments-their progression to drug resistance. Drug resistance develops from a pool of cells that survive the original treatment, called minimal residual disease. Mouse models based on tetracycline-dependent expression of transgenic oncogenes are used to imitate targeted oncogene blockade and to reproduce minimal residual disease in humans. Here we describe a novel method for generating oncogene-dependent mammary tumors using somatic transfer of transactivator-containing retroviruses into transgenic mice with tetracycline-dependent oncogenes and a method for measuring continuous mitotic activity in epithelial cells in real time.