Altered Secretory Activity of APE1/Ref-1 D148E Variants Identified in Human Patients With Bladder Cancer / 대한배뇨장애요실금학회지
International Neurourology Journal
;
: S30-S37, 2016.
Article
in English
| WPRIM
| ID: wpr-122238
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Oxidation-Reduction
/
Genetic Variation
/
Urinary Bladder
/
Urinary Bladder Neoplasms
/
Enzyme-Linked Immunosorbent Assay
/
Base Sequence
/
Polymerase Chain Reaction
/
Sequence Analysis, DNA
/
Point Mutation
/
Reverse Transcription
Limits:
Humans
Language:
English
Journal:
International Neurourology Journal
Year:
2016
Type:
Article
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