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 Qi, L. Articles by Glode, L. M. Search for Related Content PubMed PubMed Citation Articles by Qi, L. Articles by Glode, L. M.

Binding and Cytotoxicity of Conjugated and Recombinant Fusion Proteins Targeted to the Gonadotropin-Releasing Hormone Receptor

¹ Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, and ² Animal Reproduction and Biotechnology Laboratory, Department of Physiology, Colorado State University, Fort Collins, Colorado

Pokeweed antiviral protein (PAP) is a plant-derived, highly potent ribosome inactivating protein that causes inhibition of protein translation and rapid cell death. We and others have delivered this protein to various cell types, including cancer cells, using hormones to specifically target cells bearing the hormone receptor. Here, we compare binding and cytotoxicity of GnRH-PAP hormonotoxins prepared either by protein conjugation (GnRH-PAP conjugate) or through recombinant DNA technology (GnRH-PAP fusion). Although GnRH-PAP conjugate protein bound specifically to and caused cell death in cells bearing the gonadotropin-releasing hormone (GnRH) receptor, we could not detect binding or cytotoxicity using two different versions of the fusion protein in receptor-positive cells. We conclude that generation of an active GnRH-PAP fusion protein may not be feasible either because both ends of the GnRH molecule are required for receptor binding, but only the NH₂ terminus is free in the fusion protein and/or that more potent analogues of GnRH (inclusion of which is not feasible in the fusion protein) are needed for efficient targeting. In contrast, the GnRH-PAP conjugate shows promise as a novel anticancer agent, capable of targeting cancer cells expressing the GnRH receptor such as prostate, breast, ovarian, endometrial, and pancreatic cells. It may also be useful as a therapeutic agent to eliminate pituitary gonadotrophs, eliminating the need for chronic GnRH analogue administration to treat hormone-sensitive diseases.

This article has been cited by other articles:

				K. E. Ratcliffe, H. M. Fraser, R. Sellar, J. Rivier, and R. P. Millar Bifunctional Gonadotropin-Releasing Hormone Antagonist-Progesterone Analogs with Increased Efficacy and Duration of Action Endocrinology, January 1, 2006; 147(1): 571 - 579. [Abstract] [Full Text] [PDF]

				A. Nagy and A. V. Schally Targeting of Cytotoxic Luteinizing Hormone-Releasing Hormone Analogs to Breast, Ovarian, Endometrial, and Prostate Cancers Biol Reprod, November 1, 2005; 73(5): 851 - 859. [Abstract] [Full Text] [PDF]

				G. Keller, A. V. Schally, T. Gaiser, A. Nagy, B. Baker, G. Halmos, and J. B. Engel Receptors for Luteinizing Hormone Releasing Hormone Expressed on Human Renal Cell Carcinomas Can Be Used for Targeted Chemotherapy with Cytotoxic Luteinizing Hormone Releasing Hormone Analogues Clin. Cancer Res., August 1, 2005; 11(15): 5549 - 5557. [Abstract] [Full Text] [PDF]

				G S Harrison, M E Wierman, T M Nett, and L M Glode Gonadotropin-releasing hormone and its receptor in normal and malignant cells Endocr. Relat. Cancer, December 1, 2004; 11(4): 725 - 748. [Abstract] [Full Text] [PDF]