Personal History• College Degree: B.S. Brandeis University
• Medical Degree: Ph.D. New York University
• Post Doctoral Degree: Albert Einstein College of Medicine
ErbR receptors in breast and prostate cancer
Our laboratory has had a long standing interest in the modulation of the activity of the Epidermal Growth Factor Receptor (ErbB) family as a means of cancer treatment. Previous studies showed that interferons could down regulate ErbB2 receptor activity in breast and ovarian cancer. We also showed that inhibition of ErbB2 receptor synthesis in lung cancer inhibited tumorigenesis by altering interactions with other ErbB family members and their ligands. Our laboratory recently cloned a protein, Ebp1, that interacts with the ErbB3 receptor. Overexpression of this protein inhibits growth of breast and prostate cancer cells. Ebp1 interacts with the E2F transcriptional activator to inhibit transcription of cell cycle regulated genes. Ebp1 also specifically interacts with the androgen receptor in prostate cancer, leading to downregulation of androgen receptor and other AR activated genes. We are exploring the potential therapeutic use of this protein in breast and prostate cancer.
Yoo, J-Y, Wang, X-W, Rishi, A, Lessor, T, Xia, X-M, Gustafson, TA, Hamburger, AW: Interaction of the PA2G4 (EBP1) protein with ErbB-3 and regulation of this binding of Heregulin. Brit. J. Cancer, 82:683-690, 2000.
Lessor, T.J., Yoo, J.-Y., Xia, X.-M., Woodford, N., Hamburger, A.W: Ectopic expression of the ErbB-3 binding protein Ebp1 inhibits growth and induces differentiation of human breast cancer cells. J. Cell Physiol.,183:321-329, 2000.
Xia, X, Cheng, A, Lessor, T, Zhang, Y-X, Hamburger, AW: Ebp1, and ErbB-3 binding protein, interacts with Rb and affects Rb transcriptional regulation. J. Cell Physiol. 187:209-217, 2001.
Nikitakis, NG, Hamburger, A.W., Sauk, J.J: The nonsteroidal anti-inflammatory drug sulindac causes down regulation of Signal Transducer and Activator of Transcription (STAT3) in human oral squamous cell carcinoma cells. Cancer Research, 62:1004-1007, 2002.
Zhang, Y, Fondell, JD, Wang, Q, Xia, X, Cheng, A, Lu, M, Hamburger, AW: Repression of androgen receptor mediated transcription by the ErbB3-binding protein, Ebp1. Oncogene, 21:5609-5618, 2002
Xia, X, Cheng, A, Akinmade, D, Hamburger, A.W. The N terminal 23 amino acids of the p55 gamma regulatory subunit of Phosphoinositide-3 kinase binds Rb and induces cell cycle arrest. Mol. Cell. Biol. 23:1717-1725, 2003.
Zhang, Y, Woodford, N, Xia, X, Hamburger, AW. Repression of E2F1-mediated transcription by the ErbB3 binding protein Ebp1 involves histone deacetylases. Nuc.Acids Res 31:2168-2177, 2003.
Zhang, Y and Hamburger, A.W. Heregulin regulates the ability of the ErbB3 binding protein Ebp1 to bind E2F promoter elements and repress E2F mediated transcription. J. Biol. CHem. 279:26126-26133, 2004
Zhang, YZ and Hamburger, A.W., Specificity and heregulin regulation of EBp1 (ErbB3 binding protein 1) mediated repression of androgen receptor signaling. Brit. J. Cancer. 92:140-146, 2005.
Zhang, Y, Wang, X-W, Jelovac, D, Nakanishi, T, Yu, M-H, Akinmade, D, Goloubeva, O, Ross, DD, Brodie, A, Hamburger, AW. The ErbB3-binding protein Ebp1 suppresses androgen receptor mediated gene transcription and tumorigenesis of prostate cancer cells. Proc. Natl. Acad of Sci. 102:9890-9895, 2005.
Zhang, Y., Akinmade, D, Hamburger, A.W. The ErbB3 binding protein Ebp1 interacts with Sin3A to repress E2F1and AR-mediated transcription. Nucleic Acids Res 33:6024-6033, 2005.
Akinmade, D, O, Zhang, Y, Lee, M-Y, Hamburger, AW. Serine 363 phosphorylation is important in mediating Ebp1 function and protein-protein interactions. Intl. J. of Oncology 31:851-858, 2007.
Akinmade, D.,Talukder, A.H., Zhang ,Y. , Luo , W., Kumar, R.and Hamburger, A.W. Phosphorylation of the ErbB3 Binding Protein Ebp1 by p21 Activated Kinase1 (PAK1) in Breast Cancer Cells. Brit. J. of Cancer 98:1134-1140,2008.
Zhang, Y, Linn, D, Liu, Z, Melamed, J, Tavora, F, Young, CY, Burger, A.M., Hamburger, A.W. The ErbB3 Binding Protein Ebp1 mitigates the androgen independent phenotype in prostate cancer. Molecular Cancer Therapeutics 7: 3176-3186, 2008.
Zhang, Y, Lu, Y, Zhou, H, Lee, M-H , Liu, Z , Hassel , BA, Hamburger, AW. Alterations in cell growth and signaling in ErbB3 binding protein -1 (Ebp1) deficient mice. BMC Cell Biology 9: 69-81,2008.