Specific protection against breast cancers by cyclin D1 ablation

Breast cancer is the most common malignancy among women. Most of these canc ers overexpress cyclin D1, a component of the core cell-cycle machinery. We previously generated mice lacking cyclin D1 using gene targeting. Here we report that these cyclin D1-deficient mice are resistant to breast cancers induced by the neu and ras oncogenes. However, animals lacking cyclin D1 re main fully sensitive to other oncogenic pathways of the mammary epithelium, such as those driven by c-myc or Wnt-1. Our analyses revealed that, in mam mary epithelial cells, the Neu-Ras pathway is connected to the cell-cycle m achinery by cyclin D1, explaining the absolute dependency on cyclin D1 for malignant transformation in this tissue. Our results suggest that an anti-c yclin D1 therapy might be highly specific in treating human breast cancers with activated Neu-Ras pathways.