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 Mendoza, N. Articles by Wickramasinghe, D. Search for Related Content PubMed PubMed Citation Articles by Mendoza, N. Articles by Wickramasinghe, D.

Inhibition of Ligand-mediated HER2 Activation in Androgen-independent Prostate Cancer

Molecular Oncology, Genentech Inc., South San Francisco, California 94080

Hormone-independent tumor growth and metastasis are associated with increased mortality in human prostate cancer. In this study, we evaluate a potential role for ligand-mediated activation of HER2 receptor tyrosine kinase in androgen-independent prostate cancers. HER2, HER3, and epidermal growth factor receptor were detected in the androgen-independent cell line 22Rv1. Heregulin stimulation results in receptor phosphorylation and cell proliferation that is inhibited by increasing concentrations of anti-HER2 recombinant humanized monoclonal antibody (rhuMAb) 2C4. Furthermore, inhibition of tumor growth was observed in xenografts derived from 22Rv1 cells when treated with rhuMAb 2C4 in a dose-dependent manner. These studies provide a framework, both in vitro and in vivo, to examine the molecular mechanisms of ligand-driven HER2 activation in androgen-independent tumorigenesis.

This article has been cited by other articles:

				K. R. Molhoek, H. Griesemann, J. Shu, J. E. Gershenwald, D. L. Brautigan, and C. L. Slingluff Jr. Human Melanoma Cytolysis by Combined Inhibition of Mammalian Target of Rapamycin and Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor-2 Cancer Res., June 1, 2008; 68(11): 4392 - 4397. [Abstract] [Full Text] [PDF]

				J. Albanell, C. Montagut, E. T. Jones, L. Pronk, B. Mellado, J. Beech, P. Gascon, G. Zugmaier, M. Brewster, M. P. Saunders, et al. A Phase I Study of the Safety and Pharmacokinetics of the Combination of Pertuzumab (rhuMab 2C4) and Capecitabine in Patients with Advanced Solid Tumors Clin. Cancer Res., May 1, 2008; 14(9): 2726 - 2731. [Abstract] [Full Text] [PDF]

				S. D. Allen, J. T. Garrett, S. V. Rawale, A. L. Jones, G. Phillips, G. Forni, J. C. Morris, R. G. Oshima, and P. T. P. Kaumaya Peptide Vaccines of the HER-2/neu Dimerization Loop Are Effective in Inhibiting Mammary Tumor Growth In Vivo J. Immunol., July 1, 2007; 179(1): 472 - 482. [Abstract] [Full Text] [PDF]

				G. Arpino, C. Gutierrez, H. Weiss, M. Rimawi, S. Massarweh, L. Bharwani, S. De Placido, C. K. Osborne, and R. Schiff Treatment of Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer Xenografts With Multiagent HER-Targeted Therapy J Natl Cancer Inst, May 2, 2007; 99(9): 694 - 705. [Abstract] [Full Text] [PDF]

				J. S. de Bono, J. Bellmunt, G. Attard, J. P. Droz, K. Miller, A. Flechon, C. Sternberg, C. Parker, G. Zugmaier, V. Hersberger-Gimenez, et al. Open-Label Phase II Study Evaluating the Efficacy and Safety of Two Doses of Pertuzumab in Castrate Chemotherapy-Naive Patients With Hormone-Refractory Prostate Cancer J. Clin. Oncol., January 20, 2007; 25(3): 257 - 262. [Abstract] [Full Text] [PDF]

				L. Bonaccorsi, D. Nosi, M. Muratori, L. Formigli, G. Forti, and E. Baldi Altered endocytosis of epidermal growth factor receptor in androgen receptor positive prostate cancer cell lines J. Mol. Endocrinol., January 1, 2007; 38(1): 51 - 66. [Abstract] [Full Text] [PDF]

				D. B. Agus, M. S. Gordon, C. Taylor, R. B. Natale, B. Karlan, D. S. Mendelson, M. F. Press, D. E. Allison, M. X. Sliwkowski, G. Lieberman, et al. Phase I Clinical Study of Pertuzumab, a Novel HER Dimerization Inhibitor, in Patients With Advanced Cancer J. Clin. Oncol., April 10, 2005; 23(11): 2534 - 2543. [Abstract] [Full Text] [PDF]

				C. W. Gregory, Y. E. Whang, W. McCall, X. Fei, Y. Liu, L. A. Ponguta, F. S. French, E. M. Wilson, and H. S. Earp III Heregulin-Induced Activation of HER2 and HER3 Increases Androgen Receptor Transactivation and CWR-R1 Human Recurrent Prostate Cancer Cell Growth Clin. Cancer Res., March 1, 2005; 11(5): 1704 - 1712. [Abstract] [Full Text] [PDF]

				P. Carter, L. Smith, and M. Ryan Identification and validation of cell surface antigens for antibody targeting in oncology Endocr. Relat. Cancer, December 1, 2004; 11(4): 659 - 687. [Abstract] [Full Text] [PDF]

				C. D. Britten Targeting ErbB receptor signaling: A pan-ErbB approach to cancer Mol. Cancer Ther., October 1, 2004; 3(10): 1335 - 1342. [Abstract] [Full Text] [PDF]

				R. Nahta, M.-C. Hung, and F. J. Esteva The HER-2-Targeting Antibodies Trastuzumab and Pertuzumab Synergistically Inhibit the Survival of Breast Cancer Cells Cancer Res., April 1, 2004; 64(7): 2343 - 2346. [Abstract] [Full Text] [PDF]

				E. K. Rowinsky Signal Events: Cell Signal Transduction and Its Inhibition in Cancer Oncologist, December 1, 2003; 8(90003): 5 - 17. [Abstract] [Full Text] [PDF]

				E. K. Rowinsky Challenges of Developing Therapeutics That Target Signal Transduction in Patients With Gynecologic and Other Malignancies J. Clin. Oncol., May 15, 2003; 21(90100): 175s - 186. [Abstract] [Full Text] [PDF]