Role of endothelin axis in progression to aggressive phenotype of prostate adenocarcinoma

Geeta Godara, Grant W. Cannon, Glenn M. Cannon, Robert R. Bies, Joel B. Nelson, Beth R. Pflug

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

BACKGROUND. Mitogenic and anti-apoptotic actions of endothelin-1 (ET-1) are mediated through endothelin A (ETA) receptors. We investigated endothelin receptor expression in increasingly aggressive phenotype and in vivo effects of combination therapy using ETA antagonist with paclitaxel. METHODS. Dunning prostate cancer cells ranged in aggressiveness from non-tumorigenic G, to tumorigenic, non-metastatic AT-1, and to tumorigenic and metastatic MLL. Binding assays were performed alongside Q-PCR to assess receptor density. MLL xenografts were treated with vehicle, atrasentan, paclitaxel, and paclitaxel+atrasentan. RESULTS. Saturation binding assays demonstrated endothelin receptor density of MLL and AT-1 cells seven- and threefold higher than G cells, respectively. Q-PCR showed 9- and 4.5-fold greater ETA mRNA expression in MLL and AT-1 than G cells, respectively and no endothelin receptor B (ETB) expression. Combination therapy had significant effect on reduction of tumor volume than paclitaxel or atrasentan alone. CONCLUSIONS. ETA expression increases in aggressive prostate carcinoma. ETA blockade combined with paclitaxel may reduce tumor growth in advanced prostate carcinoma.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalProstate
Volume65
Issue number1
DOIs
StatePublished - Sep 15 2005

Keywords

  • Atrasentan
  • Endothelin receptor A (ET)
  • Endothelin receptor B (ET)
  • Endothelin-1
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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