Overexpression of transforming growth factor ß1 in malignant prostate cells is partly caused by a runaway of TGF-ß1 auto-induction mediated through a defective recruitment of protein phosphatase 2A by TGF-ß type I receptor.
Urology
; 76(6): 1519.e8-13, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-21030067
ABSTRACT
OBJECTIVES:
To elucidate the mechanism of transforming growth factor (TGF)-ß1 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-ß type I receptor (TßRI) was monitored by coimmunoprecipitation. Blockade of TGF-ß1 signaling in cells was accomplished either by using TGF-ß-neutralizing monoclonal antibody or by transduction of a dominant negative TGF-ß type II receptor retroviral vector.RESULTS:
Basal levels of TGF-ß1 in malignant cells were significantly higher than those in benign cells. Blockade of TGF-ß signaling resulted in a significant decrease in TGF-ß1 expression in malignant cells, but not in benign cells. Upon TGF-ß1 treatment (10 ng/mL), TGF-ß1 expression was increased in malignant cells, but not in benign cells. This differential TGF-ß1 auto-induction between benign and malignant cells correlated with differential activation of extracellular signal-regulated kinase (ERK). Following TGF-ß1 treatment, the activity of serine/threonine phosphatase and recruitment of PP2A-Bα by TßRI 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-ß1 auto-induction after TGF-ß1 (10 ng/mL) treatment.CONCLUSIONS:
These results suggest that TGF-ß1 overexpression in malignant cells is caused, at least in part, by a runaway of TGF-ß1 auto-induction through ERK activation because of a defective recruitment of PP2A-Bα by TßRI.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Adenocarcinoma
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Regulação Neoplásica da Expressão Gênica
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Proteínas Serina-Treonina Quinases
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Receptores de Fatores de Crescimento Transformadores beta
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Proteína Quinase 1 Ativada por Mitógeno
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Proteína Quinase 3 Ativada por Mitógeno
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Fator de Crescimento Transformador beta1
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Proteína Fosfatase 2
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Proteínas de Neoplasias
Limite:
Humans
/
Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article