LINE-1 ORF1 Protein Is Up-regulated by Reactive Oxygen Species and Associated with Bladder Urothelial Carcinoma Progression

Cancer Genomics Proteomics. 2018 Mar-Apr;15(2):143-151. doi: 10.21873/cgp.20072.

Abstract

Background/aim: Reactivation of long interspersed nuclear element-1 (LINE-1) and oxidative stress are suggested to have oncogenic potential to drive tumorigenesis and cancer progression. We previously demonstrated that reactive oxygen species (ROS) caused hypomethylation of LINE-1 elements in bladder cancer cells. In this study, we investigated the expression of LINE-1-encoded protein (ORF1p) and oxidative stress marker 4-hydroxynonenal (4-HNE) in human bladder cancer tissues, as well as induction of ORF1p expression by ROS in bladder cancer cell lines.

Materials and methods: Thirty-six cancerous and 15 non-cancerous adjacent tissues were immunohistochemically stained for ORF1p and 4-HNE. ORF1p expression and cell migration were determined in bladder cancer cells exposed to H2O2 Results: ORF1p and 4-HNE expression was higher in cancerous than non-cancerous tissues. Elevated ORF1p expression was associated with increased 4-HNE expression and with advanced tumors. H2O2 provoked oxidative stress and up-regulated ORF1p expression in VM-CUB-1 compared to the untreated control, and to a lesser degree in TCCSUP. H2O2 exposure enhanced cell migration in UM-UC-3, TCCSUP and VM-CUB-1.

Conclusion: Elevated ORF1p expression is associated with tumor progression. ROS experimentally induce ORF1p expression and promote migration in bladder cancer cells.

Keywords: 4-HNE; LINE-1; ORF1p; bladder cancer; cancer progression; immunohistochemistry; oxidative stress.

MeSH terms

  • Aged
  • Cell Movement / physiology
  • Disease Progression
  • Female
  • Humans
  • Long Interspersed Nucleotide Elements*
  • Male
  • Proteins / genetics
  • Proteins / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Up-Regulation
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • ORF1 protein, human
  • Proteins
  • Reactive Oxygen Species