Inducible transgenics. New lessons on events governing the induction and commitment in mammary tumorigenesis

Breast cancer arises from multiple genetic events that together contribute to the established, irreversible malignant phenotype. The development of in ducible tissue-specific transgenics has allowed a careful dissection of the events required for induction and subsequent maintenance of tumorigenesis. Mammary gland targeted expression of oncogenic Ras or c-Myc is sufficient far the induction of mammary gland tumorigenesis in the rodent, and when ov erexpressed together the rate of tumor onset is substantially enhanced. In an exciting recent finding, D'Cruz et al discovered tetracycline-regulated c-Myc overexpression in the mammary gland induced invasive mammary tumors t hat regressed upon withdrawal of c-Myc expression. Almost one-half of the c -Myc-induced tumors harbored K-ras or N-ras gene point mutations, correlati ng with tumor persistence on withdrawal of c-Myc transgene expression. Thes e findings suggest maintenance of tumorigenesis may involve a second mutati on within the Ras pathway.