ArticleMolecular carcinogenesis2018
Differentiation-associated urothelial cytochrome P450 oxidoreductase predicates the xenobiotic-metabolizing activity of "luminal" muscle-invasive bladder cancers.
Article in Molecular carcinogenesis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- The Bladder as a Target for PCB Toxicity: Evidence from PCB Levels, Phase I Metabolite Levels, and Cytochrome P450 Expression Following Developmental Exposure to a Human-Relevant PCB Mixture in Mice.Chemical research in toxicology · 2026Article
- Identification and single-cell analysis of prognostic genes related to mitochondrial and neutrophil extracellular traps in bladder cancer.Scientific reports · 2025Article
- The urothelial gene regulatory network: understanding biology to improve bladder cancer management.Oncogene · 2024Review
- DNA methylation in peripheral blood leukocytes for the association with glucose metabolism and invasive breast cancer.Clinical epigenetics · 2023Article
- Metabolic Activation of Benzo[International journal of molecular sciences · 2022Article
- Procarcinogen Activation and Mutational Signatures Model the Initiation of Carcinogenesis in Human Urothelial Tissues In Vitro.European urology · 2020Article
- Bioactivation of the tobacco carcinogens 4-aminobiphenyl (4-ABP) and 2-amino-9H-pyrido[2,3-b]indole (AαC) in human bladder RT4 cells.Archives of toxicology · 2019Article
- Article
- Method for Biomonitoring DNA Adducts in Exfoliated Urinary Cells by Mass Spectrometry.Analytical chemistry · 2018Article
- Differentiation-associated urothelial cytochrome P450 oxidoreductase predicates the xenobiotic-metabolizing activity of "luminal" muscle-invasive bladder cancers.Molecular carcinogenesis · 2018Article
- Article
- Identification of miR-200c and miR141-Mediated lncRNA-mRNA Crosstalks in Muscle-Invasive Bladder Cancer Subtypes.Frontiers in genetics · 2018Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Extra-hepatic metabolism of xenobiotics by epithelial tissues has evolved as a self-defence mechanism but has potential to contribute to the local activation of carcinogens. Bladder epithelium (urothelium) is bathed in excreted urinary toxicants and pro-carcinogens. This study reveals how differentiation affects cytochrome P450 (CYP) activity and the role of NADPH:P450 oxidoreductase (POR). CYP1A1 and CYP1B1 transcripts were inducible in normal human urothelial (NHU) cells maintained in both undifferentiated and functional barrier-forming differentiated states in vitro. However, ethoxyresorufin O-deethylation (EROD) activity, the generation of reactive BaP metabolites and BaP-DNA adducts, were predominantly detected in differentiated NHU cell cultures. This gain-of-function was attributable to the expression of POR, an essential electron donor for all CYPs, which was significantly upregulated as part of urothelial differentiation. Immunohistology of muscle-invasive bladder cancer (MIBC) revealed significant overall suppression of POR expression. Stratification of MIBC biopsies into "luminal" and "basal" groups, based on GATA3 and cytokeratin 5/6 labeling, showed POR over-expression by a subgroup of the differentiated luminal tumors. In bladder cancer cell lines, CYP1-activity was undetectable/low in basal POR
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