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Role of endothelin axis in progression to aggressive phenotype of prostate adenocarcinoma
Author(s) -
Godara Geeta,
Can Grant W.,
Can Glenn M.,
Bies Robert R.,
Nelson Joel B.,
Pflug Beth R.
Publication year - 2005
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20252
Subject(s) - prostate , medicine , phenotype , prostate cancer , adenocarcinoma , endothelin 1 , endothelin receptor , prostate adenocarcinoma , oncology , pathology , cancer research , endocrinology , biology , cancer , receptor , gene , genetics
BACKGROUND Mitogenic and anti‐apoptotic actions of endothelin‐1 (ET‐1) are mediated through endothelin A (ET A ) receptors. We investigated endothelin receptor expression in increasingly aggressive phenotype and in vivo effects of combination therapy using ET A 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 ET A mRNA expression in MLL and AT‐1 than G cells, respectively and no endothelin receptor B (ET B ) expression. Combination therapy had significant effect on reduction of tumor volume than paclitaxel or atrasentan alone. CONCLUSIONS ET A expression increases in aggressive prostate carcinoma. ET A blockade combined with paclitaxel may reduce tumor growth in advanced prostate carcinoma. © 2005 Wiley‐Liss, Inc.