Radiation and the Apo2L/TRAIL apoptotic pathway preferentially inhibit thecolonization of premalignant human breast cells overexpressing cyclin D1

The role of cyclin D1 overexpression in human breast premalignancy was inve stigated using immortal, nontumorigenic MCF-10A cells. Previous work docume nted that cyclin D1 overexpression promoted in vitro anchorage-independent colonization. We now report that the colonization of MCF-10A cyclin D1 tran sfectants was preferentially inhibited by gamma-radiation and specific clas ses of apoptosis inducers [Apo-2 Ligand (Apo-2L), but not tumor necrosis fa ctor ct]. Antibody inhibition studies and semiquantitative PCR indicated th at radiation inhibition of colonization was partially mediated via the Apo2 L/TRAIL pathway. The apoptotic removal of cyclin D1-overexpressing, coloniz ation-competent premalignant breast cells by Apo2L/TRAIL or other biologica ls may represent a novel approach to the prevention of breast cancer.