| Overexpression of transforming growth factor β1 in malignant prostate cells is partly caused by a runaway of TGF-β1 auto-induction mediated through a defective recruitment of protein phosphatase 2A by TGF-β type I receptor. | |
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MedLine Citation:
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PMID: 21030067 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: To elucidate the mechanism of transforming growth factor (TGF)-β1 overexpression in prostate cancer cells. METHODS: Malignant (PC3, DU145) and benign (RWPE1, BPH1) prostate epithelial cells were used. Phosphatase activity was measured using a commercial kit. Recruitment of the regulatory subunit, Bα, of protein phosphatase 2A (PP2A-Bα) by TGF-β type I receptor (TβRI) was monitored by coimmunoprecipitation. Blockade of TGF-β1 signaling in cells was accomplished either by using TGF-β-neutralizing monoclonal antibody or by transduction of a dominant negative TGF-β type II receptor retroviral vector. RESULTS: Basal levels of TGF-β1 in malignant cells were significantly higher than those in benign cells. Blockade of TGF-β signaling resulted in a significant decrease in TGF-β1 expression in malignant cells, but not in benign cells. Upon TGF-β1 treatment (10 ng/mL), TGF-β1 expression was increased in malignant cells, but not in benign cells. This differential TGF-β1 auto-induction between benign and malignant cells correlated with differential activation of extracellular signal-regulated kinase (ERK). Following TGF-β1 treatment, the activity of serine/threonine phosphatase and recruitment of PP2A-Bα by TβRI increased in benign cells, but not in malignant cells. Inhibition of PP2A in benign cells resulted in an increase in ERK activation and in TGF-β1 auto-induction after TGF-β1 (10 ng/mL) treatment. CONCLUSIONS: These results suggest that TGF-β1 overexpression in malignant cells is caused, at least in part, by a runaway of TGF-β1 auto-induction through ERK activation because of a defective recruitment of PP2A-Bα by TβRI. |
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Authors:
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Nengwang Yu; James M Kozlowski; Irwin I Park; Lin Chen; Qiang Zhang; Danfeng Xu; Jennifer A Doll; Susan E Crawford; Charles B Brendler; Chung Lee |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-10-27 |
Journal Detail:
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Title: Urology Volume: 76 ISSN: 1527-9995 ISO Abbreviation: Urology Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-06 Completed Date: 2011-01-04 Revised Date: 2013-05-27 |
Medline Journal Info:
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Nlm Unique ID: 0366151 Medline TA: Urology Country: United States |
Other Details:
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Languages: eng Pagination: 1519.e8-13 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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metabolism*,
pathology Autocrine Communication Cell Line, Tumor / metabolism Enzyme Activation Gene Expression Regulation, Neoplastic* Humans Male Mitogen-Activated Protein Kinase 1 / metabolism* Mitogen-Activated Protein Kinase 3 / metabolism* Neoplasm Proteins / metabolism* Phosphorylation Prostate / metabolism Prostatic Neoplasms / metabolism*, pathology Protein Phosphatase 2 / metabolism* Protein Processing, Post-Translational Protein-Serine-Threonine Kinases / metabolism* RNA, Messenger / biosynthesis, genetics RNA, Neoplasm / biosynthesis, genetics Receptors, Transforming Growth Factor beta / metabolism* Reverse Transcriptase Polymerase Chain Reaction Transforming Growth Factor beta1 / biosynthesis*, genetics |
| Grant Support | |
ID/Acronym/Agency:
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P50 CA090386-06A2/CA/NCI NIH HHS; P50CA90386/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Neoplasm Proteins; 0/PPP2R2A protein, human; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/Receptors, Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; EC 2.7.1.11/TGF-beta type I receptor; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 3.1.3.16/Protein Phosphatase 2 |
| Comments/Corrections | |
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