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

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.

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 H2O2Results: 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. H2O2provoked oxidative stress and up-regulated ORF1p expression in VM-CUB-1 compared to the untreated control, and to a lesser degree in TCCSUP. H2O2exposure enhanced cell migration in UM-UC-3, TCCSUP and VM-CUB-1.

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

Cancer genomics & proteomics. 0000 Jan [Epub]

Patcharawalai Whongsiri, Chaowat Pimratana, Udomsak Wijitsettakul, Depicha Jindatip, Anapat Sanpavat, Wolfgang A Schulz, Michèle J Hoffmann, Wolfgang Goering, Chanchai Boonla

Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Division of Urology, Buriram Hospital, Buriram, Thailand., Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Department of Urology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Department of Pathology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand .