XRCC3 over-expressing MCF7 cells: Effect of a DNA repair associated gene with metastatic process

MARTINEZ MARIGNAC VERONICA; DAVID DAVIDSON; WILLIAM D. FOULKES; ALOYZ R.

Cartagena

Congreso; I Latin American Congress of Human Genetics and IX Colombian Congress of Genetics; 2008

RELAGH, Asociacion Colombiana de Sociedades Cientificas

Over-expression of DNA repair genes has been associated with a high resistant phenotype to radiation and antitumor agents such as cisplatin. It has been recently proposed that over-expression of DNA repair genes could provide a better background for a high metastatic behaviour of different tumour cells. In the present work, we study on the MCF7 cell line the effects of Xrcc3 over-expression on cell adhesion, cell motility and resistance to antitumor agents. Cell survival assay (SRB) was used to assess drugs resistance and adhesion features.. Basal expression level of proteins related with the cell-matrix adhesion process was characterised by Western blots and zymogram assays. Previous studies showed that the Xrcc3 over-expressing cells are highly resistant to cisplatin, a platinum-based compound that causes cross-linking of DNA and double strand breaks. Here, we show that they are also resistant to MP470, multi-targeted tyrosine kinase inhibitor (TKI), and to Dasatinib a tyrosine kinase inhibitor, and do not show any difference from the mock cells to Taxol, an inhibitor of microtubule breakdown during cell division. It has been demonstrated that dasatinib inhibits migration and invasion in different cancer cell lines. We decided to test the effect of Xrcc3 over-expression on cell adhesion and motility. Xrcc3 over-expressing MCF7 cells show a higher cell-matrix adhesion (P=0.001) and a lower motility (P=0.04) than their mock counterpart. In addition, Xrcc3 over-expressing cells show a significant higher expression of p53 (P