Decreased Expression of the Early Mitotic Gene CHFR Contributes to the Acquisition of Breast Cancer Phenotypes
Annual rept. 6 Feb 2006-5 Feb 2007
MICHIGAN UNIV ANN ARBOR
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The purpose of this study was to determine if CHFR was biologically relevant to breast cancer characteristics and progression. Here we studied both breast cancer cell lines and primary samples from breast cancer patients to investigate CHFR as a relevant tumor suppressor in breast cancer and to associate CHFR expression with clinical and pathological variables. A large percentage of samples demonstrated negative or weak CHFR protein expression or staining. In addition lack of CHFR detection correlated with increased tumor size in patients and was weakly associated with ER-negative primary tumors. To study the effects of low CHFR expression in vitro we decreased CHFR gene expression in mammary epithelial cells. Notably this resulted in the acquisition of many phenotypes associated with malignant progression including higher growth rates increased mitotic index enhanced cellular invasion and motility morphological changes and aneuploidy. Considering the association between CHFR expression and breast cancer tumor size the in vitro data presented here and its previously published correlation with cellular response to chemotherapeutics such as Taxol this study provides substantial evidence to identify CHFR as an important tumor suppressor in breast cancer and possibly a biomarker for tumor response to microtubule-targeting drugs like Taxol.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research