Altered Secretory Activity of APE1/Ref-1 D148E Variants Identified in Human Patients With Bladder Cancer

• Published in: International neurourology journal Vol. 20; no. Suppl 1; pp. S30 - 37
• Main Authors: Lee, Yu Ran, Lim, Jae Sung, Shin, Ju Hyun, Choi, Sunga, Joo, Hee Kyoung, Jeon, Byeong Hwa
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Continence Society 01.05.2016; 대한배뇨장애요실금학회
• Subjects: Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 (APE1/Ref-1); Bladder Cancer; Enzyme-Linked Immunosorbent Assay; Original; Point Mutation; Secretion; 비뇨기과학; Point Mutation; Bladder Cancer; Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 (APE1/Ref-1); Enzyme-Linked Immunosorbent Assay; Secretion
• ISSN: 2093-6931; 2093-4777; 2093-6931
• DOI: 10.5213/inj.1632600.300

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. 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. 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. 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.