This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Chen, A. Articles by Koch, Y. Search for Related Content PubMed PubMed Citation Articles by Chen, A. Articles by Koch, Y.

Two Forms of Gonadotropin-releasing Hormone (GnRH) Are Expressed in Human Breast Tissue and Overexpressed in Breast Cancer

A Putative Mechanism for the Antiproliferative Effect of GnRH by Down-Regulation of Acidic Ribosomal Phosphoproteins P1 and P2¹

Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100 [A. C., S. R., N. B-A., Y. K.], and Department of Pathology, Rabin Medical Center, Petah-Tikva 49100 [E. K., E. O.], Israel

Gonadotropin-releasing hormone (GnRH) analogues are used for the treatment of breast, prostate, and ovarian cancer. These analogues exert their antitumor effects indirectly by inhibiting the pituitary-gonadal axis, as well as by direct inhibition of proliferation of human breast cancer cells. However, the molecular mechanisms mediating these direct antiproliferative effects are not fully understood. We found that normal and malignant human breast tissue express two forms of the neuropeptide GnRH. Quantitative reverse transcription-PCR shows that mRNA encoding the GnRH-I and GnRH-II peptides are overexpressed in cancerous versus normal tissues obtained from the same patients. To elucidate the function of these peptides in breast cancer cells, we used the atlas human cDNA expression arrays technology and studied the differentially regulated genes after GnRH treatment of MCF-7 cells. We found that a wide range of GnRH-I or GnRH-II concentrations (0.1–10 nM) inhibit the expression of mRNA encoding the 60S acidic ribosomal phosphoproteins, P1 and P2. These results were confirmed by quantitative reverse transcription-PCR, as well as Western blot analysis and immunofluorescence staining. The P1 and P2 proteins interact with elongation factors EF1 and EF2, and the level of their phosphorylation is one of the regulatory mechanisms for the overall rate of protein elongation. Thus, reduced expression of P1 and P2 proteins can affect the rate of protein translation, thereby decreasing proliferation rate of cells. Our studies may therefore suggest a putative mechanism for the direct antiproliferative effect of GnRH in breast cancer cells.

This article has been cited by other articles:

				D.-K. Kim, J. S. Yang, K. Maiti, J.-I. Hwang, K. Kim, D. Seen, Y. Ahn, C. Lee, B.-C. Kang, H. B. Kwon, et al. A Gonadotropin-Releasing Hormone-II Antagonist Induces Autophagy of Prostate Cancer Cells Cancer Res., February 1, 2009; 69(3): 923 - 931. [Abstract] [Full Text] [PDF]

				I.-S. Hong, A. P. Cheung, and P. C. K. Leung Gonadotropin-Releasing Hormones I and II Induce Apoptosis in Human Granulosa Cells J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 3179 - 3185. [Abstract] [Full Text] [PDF]

				R. Lopez de Maturana, A. J. Pawson, Z.-L. Lu, L. Davidson, S. Maudsley, K. Morgan, S. P. Langdon, and R. P. Millar Gonadotropin-Releasing Hormone Analog Structural Determinants of Selectivity for Inhibition of Cell Growth: Support for the Concept of Ligand-Induced Selective Signaling Mol. Endocrinol., July 1, 2008; 22(7): 1711 - 1722. [Abstract] [Full Text] [PDF]

				S Darby, J Stockley, M M Khan, C N Robson, H Y Leung, and V J Gnanapragasam Expression of GnRH type II is regulated by the androgen receptor in prostate cancer Endocr. Relat. Cancer, September 1, 2007; 14(3): 613 - 624. [Abstract] [Full Text] [PDF]

				E. L. Baldwin, I. N. Wegorzewska, M. Flora, and T. J. Wu Regulation of Type II Luteinizing Hormone-Releasing Hormone (LHRH-II) Gene Expression by the Processed Peptide of LHRH-I, LHRH-(1-5) in Endometrial Cells Experimental Biology and Medicine, January 1, 2007; 232(1): 146 - 155. [Abstract] [Full Text] [PDF]

				A. R Gunthert, C. Grundker, A. Olota, J. Lasche, N. Eicke, and G. Emons Analogs of GnRH-I and GnRH-II inhibit epidermal growth factor-induced signal transduction and resensitize resistant human breast cancer cells to 4OH-tamoxifen Eur. J. Endocrinol., October 1, 2005; 153(4): 613 - 625. [Abstract] [Full Text] [PDF]

				K. Maiti, D. Y. Oh, J. S. Moon, S. Acharjee, J. H. Li, D. G. Bai, H.-S. Park, K. Lee, Y. C. Lee, N. C. Jung, et al. Differential Effects of Gonadotropin-Releasing Hormone (GnRH)-I and GnRH-II on Prostate Cancer Cell Signaling and Death J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4287 - 4298. [Abstract] [Full Text] [PDF]

				C. K. Cheng and P. C. K. Leung Molecular Biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Their Receptors in Humans Endocr. Rev., April 1, 2005; 26(2): 283 - 306. [Abstract] [Full Text] [PDF]

				C. K. Cheng, R. L. C. Hoo, B. K. C. Chow, and P. C. K. Leung Functional Cooperation between Multiple Regulatory Elements in the Untranslated Exon 1 Stimulates the Basal Transcription of the Human GnRH-II Gene Mol. Endocrinol., July 1, 2003; 17(7): 1175 - 1191. [Abstract] [Full Text] [PDF]

				V. D. Dixit, R. Sridaran, M. A. Edmonsond, D. Taub, and W. E. Thompson Gonadotropin-Releasing Hormone Attenuates Pregnancy-Associated Thymic Involution and Modulates the Expression of Antiproliferative Gene Product Prohibitin Endocrinology, April 1, 2003; 144(4): 1496 - 1505. [Abstract] [Full Text] [PDF]