This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xia, G. Articles by Gill, P. S. Search for Related Content PubMed PubMed Citation Articles by Xia, G. Articles by Gill, P. S.

EphB4 Expression and Biological Significance in Prostate Cancer

Departments of ¹ Medicine, ² Pathology, ³ Surgery, ⁴ Urology, and ⁵ Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine; ⁶ VasGene Therapeutics, Inc., Los Angeles, California; and ⁷ Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, New South Wales, Australia

Requests for reprints: Parkash S. Gill, USC/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, NOR 6332, Los Angeles, CA 90033-9172. Phone: 323-865-3909; Fax: 323-865-0092; E-mail: parkashg{at}usc.edu.

Prostate cancer is the most common cancer in men. Advanced prostate cancer spreading beyond the gland is incurable. Identifying factors that regulate the spread of tumor into the regional nodes and distant sites would guide the development of novel diagnostic, prognostic, and therapeutic targets. The aim of our study was to examine the expression and biological role of EphB4 in prostate cancer. EphB4 mRNA is expressed in 64 of 72 (89%) prostate tumor tissues assessed. EphB4 protein expression is found in the majority (41 of 62, 66%) of tumors, and 3 of 20 (15%) normal prostate tissues. Little or no expression was observed in benign prostate epithelial cell line, but EphB4 was expressed in all prostate cancer cell lines to varying degrees. EphB4 protein levels are high in the PC3 prostate cancer cell line and several folds higher in a metastatic clone of PC3 (PC3M) where overexpression was accompanied by EphB4 gene amplification. EphB4 expression is induced by loss of PTEN, p53, and induced by epidermal growth factor/epidermal growth factor receptor and insulin-like growth factor-I/insulin-like growth factor-IR. Knockdown of the EphB4 protein using EphB4 short interfering RNA or antisense oligodeoxynucleotide significantly inhibits cell growth/viability, migration, and invasion, and induces apoptosis in prostate cancer cell lines. Antisense oligodeoxynucleotide targeting EphB4 in vivo showed antitumor activity in murine human tumor xenograft model. These data show a role for EphB4 in prostate cancer and provide a rationale to study EphB4 for diagnostic, prognostic, and therapeutic applications.

This article has been cited by other articles:

				E. J. Yavrouian, U. K. Sinha, D. H. Rice, M. T. Salam, P. S. Gill, and R. Masood The Significance of EphB4 and EphrinB2 Expression and Survival in Head and Neck Squamous Cell Carcinoma Arch Otolaryngol Head Neck Surg, September 1, 2008; 134(9): 985 - 991. [Abstract] [Full Text] [PDF]

				S. B. Gendreau, R. Ventura, P. Keast, A. D. Laird, F. M. Yakes, W. Zhang, F. Bentzien, B. Cancilla, J. Lutman, F. Chu, et al. Inhibition of the T790M Gatekeeper Mutant of the Epidermal Growth Factor Receptor by EXEL-7647 Clin. Cancer Res., June 15, 2007; 13(12): 3713 - 3723. [Abstract] [Full Text] [PDF]

				F. Diehl, L. Rossig, A. M. Zeiher, S. Dimmeler, and C. Urbich The histone methyltransferase MLL is an upstream regulator of endothelial-cell sprout formation Blood, February 15, 2007; 109(4): 1472 - 1478. [Abstract] [Full Text] [PDF]

				G. Castellano, J. F. Reid, P. Alberti, M. L. Carcangiu, A. Tomassetti, and S. Canevari New Potential Ligand-Receptor Signaling Loops in Ovarian Cancer Identified in Multiple Gene Expression Studies Cancer Res., November 15, 2006; 66(22): 10709 - 10719. [Abstract] [Full Text] [PDF]

				U. K. Sinha, K. Mazhar, S. B. Chinn, V. K. Dhillon, L. Liu, R. Masood, D. H. Rice, and P. S. Gill The Association Between Elevated EphB4 Expression, Smoking Status, and Advanced-Stage Disease in Patients With Head and Neck Squamous Cell Carcinoma. Arch Otolaryngol Head Neck Surg, October 1, 2006; 132(10): 1053 - 1059. [Abstract] [Full Text] [PDF]

				V. Davalos, H. Dopeso, J. Castano, A. J. Wilson, F. Vilardell, J. Romero-Gimenez, E. Espin, M. Armengol, G. Capella, J. M. Mariadason, et al. EPHB4 and Survival of Colorectal Cancer Patients. Cancer Res., September 15, 2006; 66(18): 8943 - 8948. [Abstract] [Full Text] [PDF]

				N. Kertesz, V. Krasnoperov, R. Reddy, L. Leshanski, S. R. Kumar, S. Zozulya, and P. S. Gill The soluble extracellular domain of EphB4 (sEphB4) antagonizes EphB4-EphrinB2 interaction, modulates angiogenesis, and inhibits tumor growth Blood, March 15, 2006; 107(6): 2330 - 2338. [Abstract] [Full Text] [PDF]