by inhibiting the nuclear translocation of EGFR and HER2. PLoS One 4: e5933. 54. Roberts PJ, Der CJ (2007) Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26: 3291–3310. 55. Nahta R, Hortobagyi GN, Esteva FJ (2003) Growth factor receptors in breast cancer: potential for therapeutic intervention. Oncologist 8: 5–17. 56. Gu L, Waliany S, Kane SE (2009) Darpp-32 and its truncated variant t-Darpp have antagonistic effects on breast cancer cell growth and herceptin resistance. PLoS One 4: e6220. 57. Arteaga C (2003) Targeting HER1/EGFR: a molecular approach to cancer therapy. Semin Oncol 30: 3–14. 58. Graham DL, Hillman DW, Hobday TJ, Rousey SR, Nair SG, et al. (2005) Phase II study of erlotinib (OSI-774) plus gemcitabine as first-or second-line therapy for metastatic breast cancer (MBC); 2005. Abstract No: 644. 59. Polychronis ASH, Hadjiminas D, Singhal H, Mansi JL, Ali S, et al. (2005) Antiproliferative and molecular effects of neoadjuvant (pre-operative) gefitinib alone or in combination with anastrozole in epidermal growth factor receptor (EGFR) positive, estrogen receptor alpha (ERa) positive patients with primary breast cancer; 2005. Abstract No: 552. 60. Ciardiello FTT, Caputo F, de Laurentiis M, Tortora G, Palmieri G, de Vita F, et al. (2005) Phase II trial of gefitinib combined with docetaxel as first-line therapy in patients with metastatic breast cancer; 2005. . pp Abstract No: 3080. 61. Arteaga CL, Baselga J (2004) Tyrosine kinase inhibitors: why does the current process of clinical development not apply to them? Cancer Cell 5: 525–531. 62. Theocharis AD, Skandalis SS, Tzanakakis GN, Karamanos NK (2010) Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting. Febs J 277: 3904–3923. 63. Shimizu-Hirota R, Sasamura H, Mifune M, Nakaya H, Kuroda M, et al. (2001) Regulation of vascular proteoglycan synthesis by angiotensin II type 1 and type 2 receptors. J Am Soc Nephrol 12: 2609–2615. Versican G3 Modulates Breast Cancer Cell Apoptosis 64. Syrokou A, Tzanakakis GN, Hjerpe A, Karamanos NK (1999) Proteoglycans in human malignant mesothelioma. Stimulation of their synthesis induced by epidermal, insulin and platelet-derived growth factors involves receptors with tyrosine kinase activity. Biochimie 81: 733–744. 65. Wu Y, Chen L, Zheng PS, Yang BB (2002) beta 1-Integrin-mediated glioma cell adhesion and free radical-induced apoptosis are regulated by binding to a C- terminal domain of PG-M/versican. J Biol Chem 277: 12294–12301. 66. Aguirre-Ghiso JA, Liu D, Mignatti A, Kovalski K, Ossowski L (2001) Urokinase receptor and fibronectin regulate the ERK(MAPK) to p38(MAPK) activity ratios that determine carcinoma cell proliferation or dormancy in vivo. Mol Biol Cell 12: 863–879. 67. Frame S, Cohen P (2001) GSK3 takes centre stage more than 20 years after its discovery. Biochem J 359: 1–16. 68. Jamerson MH, Johnson MD, Dickson RB (2000) Dual regulation of proliferation and apoptosis: c-myc in bitransgenic murine mammary tumor models. Oncogene 19: 1065–1071. 69. Marshall CJ (1995) Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80: 179–185. 70. Recchia I, Rucci N, Funari A, Migliaccio S, Taranta A, et al. (2004) Reduction of c-Src activity by substituted 5,7-diphenyl-pyrrolo[2,3-d]-pyrimidines induces osteoclast apoptosis in vivo and in vitro. Involvement of ERK1/2 pathway. Bone 34: 65–79. 71. Navolanic PM, Steelman LS, McCubrey JA (2003) EGFR family signaling and its association with breast cancer development and resistance to chemotherapy (Review). Int J Oncol 22: 237–252. 72. Langlois B, Perrot G, Schneider C, Henriet P, Emonard H, et al. (2010) LRP-1 promotes cancer cell invasion by supporting ERK and inhibiting JNK signaling pathways. PLoS One 5: e11584. PLoS ONE | www.plosone.org 15 November 2011 | Volume 6 | Issue 11 | e26396