Centrosome Amplification: A Potential Marker of Breast Cancer Aggressiveness

摘要

The aim of our research is to elucidate the mechanisms by which the normal regulatory pathways coordinating centrosome duplication with cell cycle events become uncoupled. Since negative (tumor suppressors) and positive (oncogenes) regulators of cell cycle progression can also regulate centrosome duplication, we propose that in breast cancer, alterations in growth factor signaling pathways, and/or inactivation of the p53 pathway act to deregulate G1/S and/or G2/M cell cycle checkpoints. Centrosome amplification may represent an early event in breast cancer development, while the degree of amplification may also increase during tumor progression accelerating the rate of chromosomal instability and aggressiveness. These studies will have an important impact in basic and clinical oncology for two reasons: first, they will help to define the molecular mechanisms leading to centrosome amplification in breast cancer; second, they will clarify if centrosome amplification represents a driving force in selecting hormone-independent and chemoresistant clones in breast cancer and its potential role as a new suitable marker of tumor aggressiveness.