Document Detail

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.
MedLine Citation:
PMID:  21030067     Owner:  NLM     Status:  MEDLINE    
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.
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:
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:
Title:  Urology     Volume:  76     ISSN:  1527-9995     ISO Abbreviation:  Urology     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-06     Completed Date:  2011-01-04     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0366151     Medline TA:  Urology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1519.e8-13     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
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MeSH Terms
Adenocarcinoma / metabolism*,  pathology
Autocrine Communication
Cell Line, Tumor / metabolism
Enzyme Activation
Gene Expression Regulation, Neoplastic*
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / metabolism*
Neoplasm Proteins / metabolism*
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
P50 CA090386-06A2/CA/NCI NIH HHS; P50CA90386/CA/NCI NIH HHS
Reg. No./Substance:
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 type I receptor; EC Kinases; EC Protein Kinase 1; EC Protein Kinase 3; EC Phosphatase 2

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