Altered Secretory Activity of APE1/Ref-1 D148E Variants Identified in Human Patients With Bladder Cancer / 대한배뇨장애요실금학회지
International Neurourology Journal
; : S30-S37, 2016.
Article
em En
| WPRIM
| ID: wpr-122238
Biblioteca responsável:
WPRO
ABSTRACT
PURPOSE: Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA repair and redox modulation. Recently, serum and urinary APE1/Ref-1 levels were reported to be increased in patients with bladder cancer. Genetic variations of APE/Ref-1 are associated with the risk of cancer. However, the effect of APE1/Ref-1 variants on its secretory activity is yet unknown. METHODS: APE1/Ref-1 variants were evaluated by DNA sequencing analysis of reverse transcription polymerase chain reaction products in coding DNA sequences (CDS) of APE1/Ref-1 in bladder tissue samples from patients with bladder cancer (n=10). Secretory activity of APE1/Ref-1 variants was evaluated with immunoblot and enzyme-linked immunosorbent assay of the culture medium supernatants. RESULTS: Four different substitution mutants (D148E, I64V/D148E, W67R/D148E, and E86G/D148E) of APE1/Ref-1 were identified in bladder cancer specimens. However, deletion mutants of APE1/Ref-1 CDS were not found. The secretory activity of the APE1/Ref-1 variants (D148E, I64V/D148E, and E86G/D148E) was increased compared to that of wild type APE1/Ref-1. Furthermore, the secretory activity in basal or hyperacetylated conditions was much higher than that in APE1/Ref-1 D148E-transfected HEK293 cells. CONCLUSIONS: Taken together, our data suggest that the increased secretory activity of D148E might contribute to increased serum levels of APE1/Ref-1 in patients with bladder cancer.
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Texto completo:
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Base de dados:
WPRIM
Assunto principal:
Oxirredução
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Variação Genética
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Bexiga Urinária
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Neoplasias da Bexiga Urinária
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Ensaio de Imunoadsorção Enzimática
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Sequência de Bases
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Reação em Cadeia da Polimerase
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Análise de Sequência de DNA
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Mutação Puntual
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Transcrição Reversa
Limite:
Humans
Idioma:
En
Revista:
International Neurourology Journal
Ano de publicação:
2016
Tipo de documento:
Article