Abstract
The endothelins, a family of potentvasoconstricting peptides, have beenimplicated in the pathophysiology ofadvanced prostate cancer. Two endothelinreceptors, ET-A and ET-B are found innormal prostate tissue. Malignant prostatecells are notable for the loss of ET-Breceptors and increased levels ofendothelin-1 [ET-1]; this distortion of theendothelin system may be a significantfactor in the progression of prostatecancer. Proposed roles for endothelin inprostate cancer include growth promotion,apoptosis inhibition, bone formation, andstimulation of nociceptive receptors. ET-1can act alone as a mitogen, but its effectsare greatest as a comitogen with a varietyof growth factors, including basicfibroblast growth factor, insulin-likegrowth factors, and platelet derived growthfactor. Although their exact functions areunclear, ET-1, in conjunction with vascularendothelial growth factor, appears to playa major role in tumor angiogenesis. By avariety of methods, ET-1 alters the balanceof osteoblast and osteoclasts to the favornew bone formation that is characteristicof metastatic disease. Several studiesindicate that the refractory pain ofmetastatic cancer is related to the directnociceptive effects ET-1. These findingssuggest that ET receptors are promisingtherapeutic targets for pharmacologicintervention. Early clinical trialsindicate that the ET-A receptor antagonistused in prostate cancer is reasonably welltolerated with mild but pervasive symptomsrelated to ET-1's vasoconstrictive effects. Results of ongoing clinical trials areeagerly awaited in order to see if thehypothetical promise of ET antagonism willresult in clinical success.
Similar content being viewed by others
References
Xu D, Emoto N, Giaid A, Slaughter C, Kaw S, deWit D, Yanagisawa M. ECE-1: a membrane bound metalloprotease that catalyses the proteolytic activation of big endothelin-1. Cell 78: 473–485, 1994
Rubin SA, Levin ER: The endocrinology of vasoactive peptides: synthesis to function. J Clin Endocr Metabol 78: 6–10, 1994
Burkhardt M, Barton M, Shaw SG: Receptor-and non-receptor-mediated clearance of big-endothelin and endothelin-1: differential effects of acute and chronic ETA receptor blockade. J Hypertens 18: 273–279, 2000
Bremnes T, Paasche JD, Mehlum A, Sandberg C, Bremnes B, Attramadal H: Regulation and Intracellular trafficking pathways of the endothelin receptors. J Biol Chem 275: 17596–17604, 2000
Vijayaraghavan J, Scicli AG, Carretero OA, Slaughter C, Moomaw C, Hersh LB: The hydrolysis of endothelins by neutral endopeptidase. J Biol Chem 265: 14150–14155, 1990
Battistini B, D'Orleans-Juste P, Sirois P: Endothelins: circulating plasma levels and presence in other biologic fluids. Lab Invest 68: 600–628, 1993
Le Brun G, Aubin P, Soliman H, Ropiquet F, Villette J, Berthon P, Creminon C, Cussenot O, Fiet J: Upregulation of endothelin 1 and its precursor by IL-1β, TNF-α, and TCG-β in the PC3 human prostate cancer cell line. Cyto 11: 157–162, 1999
Goldie RG: Endothelins in health and disease: an overview. Clin Exp Pharmacol Physiol 26: 145–148, 1999
Lees DM, Pallikaros Z, Corder R: The p55 tumor necrosis factor receptor (CD120a) induces endothelin-1 synthesis in endothelial and epithelial cells. Eur J Pharmacol 390: 89–94, 2000
Rubanyi GM, Polokoff MA: Endothelins: molecular biology, biochemistry, pharmacology, physiology and pathophysiology. Pharmacol Rev 46: 328, 1994
Mortensen LH: Endothelin and the clinical and peripheral nervous systems: a decade of endothelin research. Clin Exp Pharmacol Physiol 26: 980–984, 1999
Chiao JW, Moonga BS, Yang YM, Kancheria R, Mittelman A, Wu-Wong JR, Ahmed T: Endothelin-1 from prostate cancer cells is enhanced by bone contact which blocks osteoclastic bone resorption. Br J Cancer 83: 360–365, 2000
Sullivan ME, Mumtaz FH, Khan MA, Dashwood MR, Thompson CS, Mikhailidis DP, Morgan RJ: Endothelins in the urinary tract. Br J Urology 86: 97–106, 2000
Shweiki D, Itin A, Soffer D, Keshet E: Vascular endothelial growth factor induced by hypoxia may mediate hypoxiainitiated angiogenesis. Nature 359: 843–845, 1992
Levy A, Levy N, Wegner S: Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem 270: 333–400, 1995
Masaki T, Miwa S, Sawamura T, Ninomiya H, Okamoto Y: Subcellular mechanisms of endothelin action in vascular system. Euro J Pharmacol 375: 133–138, 1999
Simonson MS, Herman WH: Protein kinase C and protein tyrosine kinase activity contribute to mitogenic signaling by endothelin-1. Cross-talk between G protein-coupled receptors and pp60c-src. J Biol Chem 268: 9347–9357, 1993
van Biesen T, Hawes BE, Luttrell DK, Krueger KM, Touhara K, Porfiri E, Sakaue M, Luttrell LM, Lefkowitz RJ: Receptor-tyrosine-kinase and Gbg-mediated MAP kinase activation by a common signaling pathway. Nature 376: 781–784, 1995
Daub H, Weiss FU, Wallasch U, Ullrich A: Role of transactivation of the EGF receptor in signaling by G-protein coupled receptors. Nature 379: 557–560, 1996
Tsukahara H, Ende H, Magazine H, Bahou W, Goligorsky MS: Molecular and functional characterization of the non-selective ET-B receptor in endothelial cells. J Biol Chem 269: 21778–21785, 1994
Owada A, Tomita K, Terada Y, Sakamoto H, Nonoguchi H, Marumo F: Endothelin (ET)-3 stimulates cyclic guanosine 3',5'-monophosphate production via ETB receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells. J Clin Invest 93: 556–563, 1994
Warner TD, de Nucci G, Vane JR: Rat endothelin is a vasodilator in the isolated perfused mesentery of the rat. Eur J Pharmacol 159: 325–326, 1989
Hirata Y, Emori T, Eguchi S, Kanno K, Imai T, Ohta K, Marumo F: Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. J Clin Invest 91: 1367–1373, 1993
Verhaar MC, Strachan FE, Newby DE, Cruden NL, Koomans HA, Rabelink TJ, Webb DJ: Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade. Circulation 97: 752–756, 1998
Goligorski MS, Tsukahara H, Magazine H, Anderson TT, Malik AB, Bahou WF: Termination of endothelin signaling: role of nitric oxide. J C Physiol 158: 485–494, 1994
Boulanger C, Luscher TF: Release of endothelin from the porcine aorta: inhibition by endothelin-derived nitric oxide. J Clin Invest 85: 587–590, 1990
Yohn JJ, Smith C, Stevens T, Morelli JG, Shurnas LR, Walchak SJ, Hoffman TA, Kelley KK, Escobedo-Morse A, Yanagisawa M, Kane MA, Samora MR: Autoregulation of endothelin-1 secretion by cultured human keratinocytes via the endothelin B receptor. Biochim Biophys Acta 1224: 454–458, 1994
Fukahiro T, Fujikawa T, Ozaki S, Ishikawa K, Yano M, Nishikibi M: Clearance of circulating endothelin-1 by ETB receptors in rats. Biochem Biophys Res Commun 199: 1491–1465, 1994
Benigni A: Defining the role of endothelin in renal pathophysiology on the basis of selective and unselective endothelin receptor antagonist studies. Curr Opin Nephrol Hypertens 4: 349–353, 1995
Hartter E, Woloszczuk W: Radioimmunoassay of endothelin. Lancet 1: 909, 1989
Saito Y, Nakao K, Itoh H, Yamada T, Mukoyama M, Arai H, Hosoda K, Shirakami G, Shin-Ichi S, Jougasaki M, Morichika S, Imura H: Endothelin in human plasma and culture medium or aortic endothelial cells-detection and characterization with radioimmune assay using monoclonal antibody. Biochem Biophys Res Commun 161: 320–326, 1989
Langenstroer P, Tang R, Shapiro E, Divish B, Opgenorth T, Lepor H: Endothelin-1 in the human prostate: tissues levels, source of production and isometric tension studies. J Urol 150: 495–499, 1993
Walden PD, Ittman M, Manaco ME, Lepor H: Endothelin-1 production and agonist activities in cultured prostate-derived cells: implications for regulation of endothelin bioactivity in prostatic hyperplasia. Prostate 34: 241–250, 1993
Prayer-Galetti T, Rossi GP, Belloni AS, Albertin G, Battanello W, Piovan V, Gardiman M, Pagano F: Gene expression and autoradiographic localization of endothelin-1 and its receptors A and B in different zones of the normal prostate. J Urol 157: 2334–2339, 1997
Kobayashi S, Tang R, Wang B, Opgenorth T, Stein E, Shapiro E, Lepor H: Localization of endothelin receptors in the human prostate. J Urol 151: 763–766, 1994
Nelson JB, Chan-Tack K, Hedican SP, Magnuson SR, Opgenorth TJ, Bova GS, Simons JW: Endothelin-1 production and decreased endothelin-B receptor expression in advanced prostate cancer. Cancer Res 56: 663–668, 1996
Filep JG, Foldes-Filep E, Rousseau A, Fournier A, Sirois P, Yano M: Endotheline-1 enhances vascular permeability in the rat heart through the ET-A receptor. Eur J Pharmacol 219: 343–344, 1992
Zouki C, Baron C, Fournier A, Fielep JG: Endothelin-1 enhances neutrophil adhesion to human coronary artery endothelial cells: role of ET-A receptors and platelet-activating factor. Br J Pharmacol 127: 969–979, 1999
Helset E, Sildnes T, Selkelid R, Konopski ZS: Endothelin-1 stimulates human monocytes in vitro to release TNF-α, interleukin-β and interleukin-6. Med Inflamm 2: 417–422, 1993
Stankova J, D'Orleans-Juste P, Rola-Pleszczynki M: ET-1 induces interleukin-6 gene expression in human umbilical vein endothelial cells: synergistic effect of interleukin-1. Am J Physiol 271: C1073-C1078, 1996
Casey ML, Byrd W, MacDonald PC: Massive amounts of immunoreactive endothelin in human seminal fluid. J Clin Endocrinol Metab 74: 223–225, 1992
Nelson JB, Lee WH, Nguyen SH, Jarrard DF, Brooks JD, Magnuson SR, Opgenorth TJ, Nelson WG, Bova GS: Methylation of the 5’ CpG island of the endothelin B receptor gene is common in human prostrate cancer. Can Res 57: 35–37, 1997
Zheng H, Pflug BR, Marshall FF, Nelson JB, Brooks JD: Frequent promoter methylation of the endothelin B receptor gene ENDRB in human renal tumors. (abstract) J Urol 161: 137, 1999
Drimal J, Drimal Jr J, Drimal D: Enhanced endothelin ETB receptor down-regulation in human tumor cells. Eur J Pharmacol 396: 19–22, 2000
Kikuchi K, Nakagawa H, Kadono T, Etoh T, Byers HR, Mihm MC, Tamaki K: Decreased ET(B) receptor expression in human metastatic melanoma cells. Biochem Biophys Res Commun 219: 734–739, 1996
Alanen K, Deng DX, Chakrabarti S: Augmented expression of endothelin-1, endothelin-3 and the endothelin-B receptor in breast carcinoma. Histopathology 36: 161–167, 2000
Ahmed SI, Thompson J, Coulson JM, Woll PJ: Studies on the expression of endothelin, its receptor subtypes, and converting enzymes in lung cancer and in human bronchial epithelium. Am J Respir Cell Mol Biol 22: 422–432, 2000
Nelson JB, Hedican SP, George DJ, Reddi AH, Piantadosi S, Eisenberger MA, Simons JW: Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med 1: 944–949, 1995
Shankar A, Loizidou M, Aliev G, Fredericks S, Holt D, Boulos PB, Burnstock G, Taylor I.: Raised endothelin 1 levels in patients with colorectal liver metastases. Br J Surg 85: 502–506, 1998
Patel KV, Schrey MP: Human breast cancer cells contain a phosphoramidon-sensitive metalloproteinase which can process exogenous big endothelin-1 to endothelin-1: a proposed mitogen for human breast fibroblasts. Br J Cancer 71: 442–447, 1995
Thevarajah S, Udan M, Zheng H, Pflug BR, Nelson JB: Endothelin axis expression in renal cell carcinoma. (abstract) J Urol 161: 137, 1999
Bagnato A, Salani D, Di Castro V, Wu-Wong JR, Tecce R, Nicotra MR, Venuti A, Natali PG: Expression of endothelin 1 and endothelin A receptor in ovarian carcinoma: evidence for an autocrine role in tumor growth. Cancer Res 59: 720–727, 1999
Kanse SM, Wijelath E, Kanthou C, Newman P, Kakkar VV: The proliferative responsiveness of human vascular smooth muscle cells to endothelin correlates with endothelin receptor density. Lab Invest 72: 376–382, 1995
Ishizaka K, Azuma H, Matsubara O, Kitahara S, Oshima H: Production of endothelin by canine prostatic epithelial cells and its stimulatory effects on their growth. J Androl 50: 559–536, 1999
Daub H, Weiss FU, Wallasch C: Role of transactivation of the EGF receptor in signaling by G-protein-coupled receptors. Nature 379: 557–560, 1996
Vacca F, Bagnato A, Catt KJ, Tecce R: Transactivation of the epidermal growth factor in endothelin-1 induced mitogenic signaling in human ovarian carcinoma cells. Cancer Res 60: 5310–5317, 2000
Moraitis S, Langdon SP, Miller WR: Endothelin expression and responsiveness in human ovarian carcinoma cell lines. Eur J Cancer 33: 661–668, 1997
Pagotto U, Arzberger T, Hopfner U, Sauer J, Renner U, Newton CJ, Lange M, Uhl E, Weindl A, Stalla GK: Expression and localization of endothelin-1 and endothelin receptors in human meningiomas. Evidence for a role in tumor growth. J Clin Invest 96: 2017–2025, 1995
Bagnato A, Tecce R, Moretti C, Di Castro V, Spergel D, Catt KJ: Autocrine actions of endothelin-1 as a growth factor in human ovarian carcinoma cells. Clin Cancer Res 1:1059–1066, 1995
Kitagawa N, Tsutsumi K, Niwa M, Yamaga S, Anda T, Khalid H, Himeno A, Taniyama K, Shibata S: A selective endothelin ETA antagonist, BQ-123, inhibits 125l-endothelin-1 (125l-ET-1) binding to human meningiomas and antagonizes ET-1-induced proliferation of meningioma cells. Cell Mol Neurobiol 14: 105–118, 1994
Moraitis S, Miller WR, Smyth JF, Langdon SP: Paracrine regulation of ovarian cancer by endothelin. Eur J Cancer 35: 1381–1387, 1999
Yang Z, Krasnici N, Luscher T: Endothelin-1 potentiates human smooth muscle cell growth to PDGF. Circulation 100: 5–8, 1999
Fudge K, Bostwick DG, Stearns ME: Platelet-derived growth factor A and B chains and the alpha and beta receptors in prostatic intraephithelial neoplasia.Prostate 29: 282–286, 1996
Shawver LK, Schwartz DP, Mann E, Chen H, Tsai J, Chu L, Taylorson L, Longhi M, Meredith S, Germain L, Jacobs JS, Tang C, Ullrich A, Berens ME, Hersh E, McMahon G, Hirth KP, Powell TJ: Inhibition of platelet-derived growth factor-mediated signal transduction and tumor growth by N-[4-(trifluoromethyl)-phenyl]5-methylisoxa zole-4-carboxamide. Clin Cancer Res 3: 1167–1177, 1997
Stiles CD, Capone GT, Scher CD, Antoniades HN, Van Wyk JJ, Pledger WJ: Dual control of cell growth by somatomedins and platelet-derived growth factor. Proc Natl Acad Sci USA 76: 1279–1283, 1979
Pietrzkowski Z, Mulholland G, Gomella L, Jameson BA, Wernicke D, Baserga R: Inhibition of growth of prostatic cancer cell lines by peptide analogues of insulin-like growth factor 1. Cancer Res 53: 1102–1106, 1993
Culig Z, Hobisch A, Cronauer MV, Radmayr C, Hittmair A, Zhang J, Thurnber M, Bartsch G, Klocker H: Regulation of prostatic growth and function by peptide growth factors. Prostate 28: 392–405, 1996
Wu-Wong JR, Chiou WJ, Dickinson R, Opgenorth TJ: Endothelin attenuates apoptosis in human smooth muscle cells. Biochem J 328: 733–737, 1997
Okazawa M, Siraki T, Ninomiya H, Kobayashi S, Masaki T: Endothelin-induced apoptosis of A375 human melanoma cells. J Biol Chem 273: 12581–12592, 1998
Kitasjima I, Kawahara K, Nakajima T, Soejima Y, Matsuyama T, Maruyama I: Nitric oxide-mediated apoptosis in murine mastocytoma. Biochem Biophys Res Commun 204: 244–251, 1994
Xie K, Wang Y, Huang S, Xu L, Bielenberg D, Salas T, McConkey DJ, Jiang W, Fidler IJ: Nitric oxide-mediated apoptosis of K-1735 melanoma cells is associated with downregulation of Bcl-2. Oncogene 15: 771–779, 1997
Corasaniti MT, Melino G, Tartaglia RL, Finazzi-Agro A, Nistico G: N-methyl-D-aspartate-induced excessive formation of nitric oxide in CHP100 neuroblastoma cells produces death of BMEL melanoma cells in co-culture. Neuropharmacology 33: 1071–1077, 1994
Xie K, Huang S, Dong Z, Juang SH, Gutman M, Xie QW, Nathan C, Fidler IJ: Transfection with the inducible nitric oxide synthase gene suppresses tumorigenicity and abrogates metastasis by K-1735 murine melanoma cells. J IntMed 181: 1333–1343, 1995
Jenkins DC, Charles IG, Thomsen LL, Moss DW, Holmes LS, Baylis SA, Rhodes P, Westmore K, Emson PC, Moncada S: Roles of nitric oxide in tumor growth. Proc Natl Acad Sci USA 92: 4392–4396, 1995
Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other diseases. Nature 1: 27–31, 1995
Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J: Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 143: 401, 1993
Ziche M, Morbidelli M, Donnini S, Ledda F: ETB receptors promote proliferation and migration of endothelial cells. J Cardiovasc Pharmacol 26: S284–286, 1995
Wren A, Hiley C, Fan TP: Endothelin-3 mediated proliferation of wounded human umbilical vein endothelial cells. Biochem Biophys Res Commun 196: 369–375, 1993
Morbidelli L, Orlando C, Maggi C, Idda F, Zicke M: Proliferation and migration of endothelial cells is promoted by endothelins via activation of ET-B receptors. Am J Physiol 269: H686–695, 1995
Goligorsky MS, Budzikowski AS, Tsukahara H, Noiri E: Co-operation between endothelin and nitric oxide in promoting endothelial cell migration and angiogenesis. Clin Exp Pharmacol Physiol 26: 269–271, 1999
Pedram A, Razandi M, Hu RM, Levin ER: Vasoactive peptides modulate vascular endothelial cell growth factor production and endothelial cell proliferation and invasion. J Biol Chem 272: 17097–17103, 1997
Salani D, Di Castro V, Nicotra MR, Rosano L, Tecce R, Venuti A, Natali PG, Bagnato A: Role of Endothelin-1 in neovascularization of ovarian carcinoma. Amer J Path 157: 1537–1547, 2000
Strohmeyer D, Rossing C, Bauerfeind A, Kaufmann O, Schlechte H, Bartsch G, Loening S: Vascular endothelial growth factor and its correlation with angiogenesis and p53 expression in prostate cancer. Prostate 45: 216–224, 2000
Salani D, Garagoletti G, Rosano L, Di Castro V, Borsotti P, Giavazzi R, Bagnato A: Endothelin-1 induces an angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Amer J Path 157: 1703–1711, 2000
Takuwa Y, Ohue Y, Takuwa N: Endothelin-1 activates phospholipase C and mobilizes Ca2+ from extra-and intracellular pools in osteoblastic cells. Am J Physiol 257: E797-E803, 1989
Takuwa Y, Masaki T, Yamashita K: The effects of the endothelin family peptides on cultured osteoblastic cells from rat calvariae. Biochem Biophy Res Commun 170: 998–1005, 1990
Tatrai A, Foster S, Lakatos P, Shankar G, Stern PH: Endothelin-1 actions on resorption, collagen and noncollagen protein synthesis, and phosphatidylinositol turnover in bone organ cultures. Endocrinology 131: 603–607, 1992
Shioide M, Noda M: Endothelin modulates osteopontin and osteocalcin messenger ribonucleic acid expression in rat osteoblastic osteosarcoma cells. J Cell Biochem 53: 176–180, 1993
Alam ASMT, Gallagher A, Shankar V: Endothelin inhibits osteoclastic bone resorption by a direct effect on cell motility: implications for the vascular control of bone resorption. Endocrinology 130: 3617–3624, 1992
Nelson JB, Nguyen SH, Wu-Wong JR, Opgenorth TJ, Dixon DB, Chung LWK, Inoue N: New bone formation in an osteoblastic tumor model is increased by endothelin-1 overexpression and decreased by endothelin-A receptor blockade. Urology 53: 1063–1069, 1999
Dahlof B, Gustafsson D, Hedner T, Jern S, Hansson L: Regional haemodynamic effects of endothelin-1 in rat and man: unexpected adverse reaction. J Hypertens 8: 811–817, 1990
Davar G, Hans G, Fareed MU, Sinnott C, Strichartz G: Behavioral signs of acute pain produced by application of endothelin-1 to rat sciatic nerve. Neuroreport 9: 2279–2283, 1998
Yoshizawa T, Kimura S, Kanazawa I, Uchiyama Y, Yanagisawa M, Masaki T: Endothelin localizes in the dorsal horn and acts on the spinal cord neurons: possible involvement of dihydropyridine-sensitive calcium channels and substance P release. Neurosci Lett 102: 179–184, 1989
Dymshitz J, Vasko MR: Endothelin-1 enhances capsaicin-induced peptide release and CGMP accumulation in cultures of rat sensory neurons. Neurosci Lett 167: 128–132, 1994
De-Melo JD, Tonussi CR, D'Orleans-Juste P, Rae GA: Articular nociception by endothelin-1, carrageenan and LPS in naïve and previously inflamed knee-joints in the rat: inhibition by endothelin receptor antagonists. Pain 77: 261–269, 1998
Raffa RB, Schupsky JJ, Jacoby HI: Endothelin-induced nociception in mice: mediation by ETA and ETB receptors. J Pharmacol Exp Ther 276: 647–651, 1996
Piovezan AP, D'Orleans JP, Souza GE, Rae GA: Endothelin-1 induced ET(A) receptor-mediated nociception, hyperalgesia and oedema in the mouse hind-paw: modulation by simultaneous ET(B) receptor activation. Br J Pharmacol 129: 961–968, 2000
Yamamoto T, Shimoyama N, Asano H, Mizuguchi T: Analysis of the role of endothelin-A and endothelin-B receptors on nociceptive information transmission in the spinal cord with FR139317, and endothelin-A receptor antagonist, and sarafotoxin S6c, an endothelin-B receptor agonist. J Pharmacol Exp Ther 27: 156–163, 1994
Benigni A, Remuzzi G: Endothelin antagonists. Lancet 353: 133–138, 1999
Hosoda K, Hammer RE, Richardson JA, Greenstein-Baynash A, Che JC, Giaid A, Yanagisawa M: Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. Cell 79: 1267–1276, 1994
Greenstein-Baynash A, Hosoda K, Giaird A, Richardson JA, Emoto N, Hammer RE, Yanagisawa M: Interaction of endothelin-3 with endothelin receptor is essential for development of epidermal melanocytes and enteric neurons. Cell 79: 1277–1285, 1994
Kurihara Y, Kurihara H, Oda H, Maemura K, Nagai R, Ishikawa T, Yazaki Y: Aortic arch malformation and ventricular septal defect in mice deficient in endothelin-1. J Clin Invest 96: 293–300, 1995
Carducci MA, Bowling KM, Rogers T, Leahy TL, Nelson JB, Janus TJ, Padley RJ: Endothelin receptor antagonist, ABT-627, for prostate cancer: initial trail results. (abstract) J of Urol 161: 176, 1999
Hewage CM, Jiang L, Parkinson JA, Ramage R, Sadler IH: A linear endothelin-1 analogue: solution structure of ET-1 (Aib1,3,11,15,Nle7) by nuclear magnetic resonance spectroscopy and molecular modeling. Neurochem Intl 35: 35–45, 1999
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kopetz, E.S., Nelson, J.B. & Carducci, M.A. Endothelin-1 as a Target for Therapeutic Intervention in Prostate Cancer. Invest New Drugs 20, 173–182 (2002). https://doi.org/10.1023/A:1015630513908
Issue Date:
DOI: https://doi.org/10.1023/A:1015630513908