Investigation of Gene Expression Correlating With Centrosome Amplification in Development and Progression of Breast Cancer

摘要

We previously demonstrated that centrosome amplification correlates with chromosomal instability and loss of differentiation in breast tumors. The goal of this research is to identify genes important in breast cancer due to their association with amplified centrosomes, We determined that centrosomes are amplified prior to invasion and amplification is maintained during progression. We identified candidate genes for further investigation. Last year, we 1) measured chromosomal instability in tumors for which we have gene expression and centrosome amplification data, 2) analyzed the relationships between lymph node and estrogen receptor status, chromosomal instability and centrosome amplification, and 3) developed a collaborative study to look at centrosome amplification, chromosomal instability, and gene expression in a rat model of estrogen-induced mammary cancer. During this last reporting period we 1) demonstrated that expression of Aurora-A, a centrosome-associated kinase, correlates to Nottingham Prognostic Index in human breast tumors, 2) demonstrated that estrogen exposure leads to centrosome amplification and aurora-A over-expression prior to invasion in a rat mammary tumor model, and 3) developed a collaboration to study the effects of cyclin D1 overexpression in a mouse model and demonstrated that cyclin D1 induces centrosome amplification and aneuploidy.