| Loss of PTEN is associated with progression to androgen independence. | |
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MedLine Citation:
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PMID: 16496415 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Progression to a lethal androgen-independent (AI) stage of advanced prostate cancer is a critical clinical obstacle limiting patient survival. PTEN inactivation is frequently observed in advanced prostate cancer and correlates with a poor prognosis. However, the functional significance of PTEN inactivation in AI progression has not been demonstrated. METHODS: PTEN expression was examined in benign, hormone naïve and AI human prostate cancer specimens, and in recurrent AI Shionogi tumors. The effect of antisense oligonucleotide (ASO)-mediated PTEN downregulation in AI progression of the Shionogi tumor model was determined. RESULTS: Significantly reduced PTEN expression was observed in AI versus benign and hormone naïve prostate tumors. Seven of 14 AI Shionogi tumors exhibited marked downregulation or complete loss of PTEN. ASO-mediated PTEN inhibition reduced androgen-withdrawal induced regression of Shionogi tumors and accelerated AI progression. CONCLUSIONS: These data suggest that PTEN inactivation may play a role in progression to androgen independence. |
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Authors:
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Jerod Bertram; James W Peacock; Ladan Fazli; Alice L-F Mui; Stephen W Chung; Michael E Cox; Brett Monia; Martin E Gleave; Christopher J Ong |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: The Prostate Volume: 66 ISSN: 0270-4137 ISO Abbreviation: Prostate Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-15 Completed Date: 2006-07-05 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8101368 Medline TA: Prostate Country: United States |
Other Details:
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Languages: eng Pagination: 895-902 Citation Subset: IM |
Copyright Information:
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Copyright 2006 Wiley-Liss, Inc. |
Affiliation:
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The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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physiology Androgens / analysis, physiology* Animals Blotting, Northern Blotting, Western Disease Progression Down-Regulation Gene Expression Regulation, Neoplastic / drug effects Genes, Suppressor / physiology Humans Male Mice Mice, Inbred Strains Neoplasm Staging Oligonucleotides, Antisense / pharmacology PTEN Phosphohydrolase / genetics*, physiology* Prognosis Prostatic Neoplasms / chemistry, genetics*, physiopathology* Signal Transduction / physiology |
| Chemical | |
Reg. No./Substance:
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0/Androgens; 0/Oligonucleotides, Antisense; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 3.1.3.48/PTEN protein, human; EC 3.1.3.67/PTEN Phosphohydrolase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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