the effect of a dna repair gene on cellular invasiveness xrcc3 over-expression in breast cancer cellsdna修复基因的效应细胞侵袭性xrcc3乳腺癌细胞中表达.pdf

The Effect of a DNA Repair Gene on Cellular Invasiveness: Xrcc3 Over-Expression in Breast Cancer Cells 1 ´ 4 1 1 Veronica L. Martinez-Marignac , Amelie Rodrigue , David Davidson , Martin Couillard , Ala-Eddin 1 1 2 4 1,2,3 Al-Moustafa , Mark Abramovitz , William D. Foulkes , Jean-Yves Masson , Raquel Aloyz * 1 McGill University, Lady Davis Institute Segal Cancer Center, Jewish General Hospital, Montreal, Canada, 2 Faculty of Medicine, Program in Cancer Genetics, McGill University, Montreal, Canada, 3 Department of Oncology, McGill University, Montreal, Canada, 4 Genome Stability Laboratory, Laval University Cancer Research Center, ˆ ´ ´ Hotel-Dieu de Quebec, Quebec City, Canada Abstract Over-expression of DNA repair genes has been associated with resistance to radiation and DNA-damage induced by chemotherapeutic agents such as cisplatin. More recently, based on the analysis of genome expression profiling, it was proposed that over-expression of DNA repair genes enhances the invasive behaviour of tumour cells. In this study we present experimental evidence utilizing functional assays to test this hypothesis. We assessed the effect of the DNA repair proteins known as X-ray complementing protein 3 (XRCC3) and RAD51, to the invasive behavior of the MCF-7 luminal epithelial-like and BT20 basal-like triple negative human breast cancer cell lines. We report that stable or transient over- expression of XRCC3 but not RAD51 increased invasiveness in both cell lines in vitro. Moreover, XRCC3 over-expressing MCF-