Elucidating and Modeling Irradiation Effects on Centrosomal and Chromosomal Stability within Breast Cancer; Final rept. 15 May 2006-1 Jan 2007

摘要

Elucidating and modeling irradiation effects on centrosomal and chromosomal stability within breast cancer. Background: At the cellular level, ionizing radiation (IR) represents an empirical and reproducible insult that elicits a well characterized cellular response. Genetic alterations, cell cycle effects and IR-induced chromosomal instability are defined-byproducts of irradiation as is centrosomal amplification. The centrosome represents the major microtubule organizing center of the dividing cell and along with the nucleus, is precisely replicated during each cell cycle. It is postulated that centrosomal amplification translates into tetraploid, through mitotic catastrophe, or aneuploid, through aberrant division, daughter cells. At this tissue level, centrosomal deregulation has been identified within the majority of malignancies and is positively correlated with chromosomal instability, higher grade tumors and patient survival. At the cellular level, we would like to investigate the mitotic outcomes downstream of irradiation induced centrosomal amplification and develop a mathematical model for this process that can be translated to different genetic backgrounds and, in the future, different micro environmental cues and tissues.