Cytoplasmic ape1 expression elevated by p53 aberration may predict survival and relapse in resected non-small cell lung cancer

Heng Hsiung Wu, Ya Chiung Chu, Lee Wang, Lung Hung Tsai, Ming Ching Lee, Chi Yi Chen, Shwn Huey Shieh, Ya Wen Cheng, Huei Lee

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background. Subcellular localization of apurinic/apyrimidinic endonuclease-1/redox factor-1 (Ape1) has been demonstrated to promote lung tumor malignancy via NFjB activation. We hypothesized that increased cytoplasmic Ape1 expression might cause NF-jB activation by p53 aberration, and result in poor outcome in non-small cell lung cancer (NSCLC). Methods. Herein, knockdown of E6 or p53 and overexpression of E6 were performed in various lung cancer cells to test whether cytoplasmic Ape1 expression could be elevated by p53 aberration. To examine whether cytoplasmic Ape1 could be associated with patients' outcome, 125 lung tumors from patients with NSCLC were collected to determine Ape1 protein and mRNA expression by immunohistochemistry and real-time RT-PCR. Results. Our data showed that cytoplasmic Ape1 decreased in E6-knockdown TL-1 cells and increased in E6-overexpressed TL-4 and p53-knockdown H520 cells; and cell invasion capability was dependent on the presence of cytoplasmic Ape1. Increases in cytoplasmic Ape1 by p53 aberration may be through activation of Ape1 transcription and S-nitrosation of Ape1 protein. Kaplan-Meier and Cox models showed that patients with high cytoplasmic Ape1 had shorter cancer-specific survival (CSS) and relapse-free survival (RFS) periods than did those with low cytoplasmic Ape1. Conclusions. We suggest that cytoplasmic Ape1 expression elevated by p53 aberration may be used to predict poor survival and relapse in patients with NSCLC.

Original languageEnglish
JournalAnnals of Surgical Oncology
Volume20
Issue number3 SUPPL.
DOIs
Publication statusPublished - 2013
Externally publishedYes

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Endonucleases
Non-Small Cell Lung Carcinoma
Oxidation-Reduction
Recurrence
Survival
Neoplasms
DNA-(Apurinic or Apyrimidinic Site) Lyase
Nitrosation
Lung
Proportional Hazards Models
Real-Time Polymerase Chain Reaction
Lung Neoplasms
Proteins
Transcription Factors
Immunohistochemistry

ASJC Scopus subject areas

  • Surgery
  • Oncology
  • Medicine(all)

Cite this

Cytoplasmic ape1 expression elevated by p53 aberration may predict survival and relapse in resected non-small cell lung cancer. / Wu, Heng Hsiung; Chu, Ya Chiung; Wang, Lee; Tsai, Lung Hung; Lee, Ming Ching; Chen, Chi Yi; Shieh, Shwn Huey; Cheng, Ya Wen; Lee, Huei.

In: Annals of Surgical Oncology, Vol. 20, No. 3 SUPPL., 2013.

Research output: Contribution to journalArticle

Wu, Heng Hsiung ; Chu, Ya Chiung ; Wang, Lee ; Tsai, Lung Hung ; Lee, Ming Ching ; Chen, Chi Yi ; Shieh, Shwn Huey ; Cheng, Ya Wen ; Lee, Huei. / Cytoplasmic ape1 expression elevated by p53 aberration may predict survival and relapse in resected non-small cell lung cancer. In: Annals of Surgical Oncology. 2013 ; Vol. 20, No. 3 SUPPL.
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AU - Chu, Ya Chiung

AU - Wang, Lee

AU - Tsai, Lung Hung

AU - Lee, Ming Ching

AU - Chen, Chi Yi

AU - Shieh, Shwn Huey

AU - Cheng, Ya Wen

AU - Lee, Huei

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N2 - Background. Subcellular localization of apurinic/apyrimidinic endonuclease-1/redox factor-1 (Ape1) has been demonstrated to promote lung tumor malignancy via NFjB activation. We hypothesized that increased cytoplasmic Ape1 expression might cause NF-jB activation by p53 aberration, and result in poor outcome in non-small cell lung cancer (NSCLC). Methods. Herein, knockdown of E6 or p53 and overexpression of E6 were performed in various lung cancer cells to test whether cytoplasmic Ape1 expression could be elevated by p53 aberration. To examine whether cytoplasmic Ape1 could be associated with patients' outcome, 125 lung tumors from patients with NSCLC were collected to determine Ape1 protein and mRNA expression by immunohistochemistry and real-time RT-PCR. Results. Our data showed that cytoplasmic Ape1 decreased in E6-knockdown TL-1 cells and increased in E6-overexpressed TL-4 and p53-knockdown H520 cells; and cell invasion capability was dependent on the presence of cytoplasmic Ape1. Increases in cytoplasmic Ape1 by p53 aberration may be through activation of Ape1 transcription and S-nitrosation of Ape1 protein. Kaplan-Meier and Cox models showed that patients with high cytoplasmic Ape1 had shorter cancer-specific survival (CSS) and relapse-free survival (RFS) periods than did those with low cytoplasmic Ape1. Conclusions. We suggest that cytoplasmic Ape1 expression elevated by p53 aberration may be used to predict poor survival and relapse in patients with NSCLC.

AB - Background. Subcellular localization of apurinic/apyrimidinic endonuclease-1/redox factor-1 (Ape1) has been demonstrated to promote lung tumor malignancy via NFjB activation. We hypothesized that increased cytoplasmic Ape1 expression might cause NF-jB activation by p53 aberration, and result in poor outcome in non-small cell lung cancer (NSCLC). Methods. Herein, knockdown of E6 or p53 and overexpression of E6 were performed in various lung cancer cells to test whether cytoplasmic Ape1 expression could be elevated by p53 aberration. To examine whether cytoplasmic Ape1 could be associated with patients' outcome, 125 lung tumors from patients with NSCLC were collected to determine Ape1 protein and mRNA expression by immunohistochemistry and real-time RT-PCR. Results. Our data showed that cytoplasmic Ape1 decreased in E6-knockdown TL-1 cells and increased in E6-overexpressed TL-4 and p53-knockdown H520 cells; and cell invasion capability was dependent on the presence of cytoplasmic Ape1. Increases in cytoplasmic Ape1 by p53 aberration may be through activation of Ape1 transcription and S-nitrosation of Ape1 protein. Kaplan-Meier and Cox models showed that patients with high cytoplasmic Ape1 had shorter cancer-specific survival (CSS) and relapse-free survival (RFS) periods than did those with low cytoplasmic Ape1. Conclusions. We suggest that cytoplasmic Ape1 expression elevated by p53 aberration may be used to predict poor survival and relapse in patients with NSCLC.

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