Versican G3 Modulates Breast Cancer Cell Apoptosis Figure 5. Versican G3 domain enhanced breast cancer cell apoptosis induced by Docetaxel, while cell apoptosis was reduced when treated with Doxorubicin, or Epirubicin. a) G3-transfected and vector-transfected 4T07 cells (16105) were inoculated in 12 well culture dishes. After cultured for 12 hours, all samples were treated with 2 mM Docetaxel, 8 mM Doxorubicin, 10 mM Epirubicin, 15 mM Cyclophosphamide, or 30 mM Trastuzumab for 24 hours. Cell viability was observed by light microscopy. b) After treated with 2 mM Docetaxel, 8 mM Doxorubicin, or 10 mM Epirubicin for 2 hours, all the samples were subjected to Annexin V assays. doi:10.1371/journal.pone.0026396.g005 UTR- expressing cells appeared between these two different morphologies. G3-39 UTR- transfected cells neither promoted the extent of cell apoptosis induced by C2-ceramide or Docetaxel, nor enhanced cell survival when treated with Doxorubicin or Epirubicin (Fig S2c, S2d). Our experiments demonstrate that the sensitivity of breast cancer cells to chemotherapeutically induced apoptosis was versican G3 domain dependant. Discussion Increased activation of EGFR and dysregulated expression of versican contributes towards a more aggressive human breast cancer phenotype [15,16,49,50,51]. Targeted therapies shows considerable promise for the future of cancer treatment and much attention has been focused on developing inhibitors of the EGFR- PLoS ONE | www.plosone.org 8 November 2011 | Volume 6 | Issue 11 | e26396