Nucleophosmin in the pathogenesis of arsenic-related bladder carcinogenesis revealed by quantitative proteomics

Journal Article · Fri Jan 15 00:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.09.016· OSTI ID:21344833

Shuhui, Chen ^[1]; Yiwen, Wang ^[2]; Jueliang, Hsu ^[1]; Hongyi, Chang ^[2]; Chiyun, Wang ^[3]; Potsun, Shen ^[1]; Chiwu, Chiang ^[3]; Jingjing, Chuang ^[4]; Hungwen, Tsai ^[5]; Powen, Gu ^[6]; Fangchih, Chang ^[7]

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1. Department of Chemistry, College of Sciences, National Cheng Kung University, Tainan 701, Taiwan (China)
2. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China)
3. Graduate Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China)
4. Department of Microbiology and Immunology, National Chiayi University, Chiayi 600, Taiwan (China)
5. Department of Pathology, National Cheng Kung University Hospital, Tainan 704, Taiwan (China)
6. Department of Clinical Pathology, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China)
7. Instrument Center, National Cheng Kung University, Tainan 701, Taiwan (China)

To investigate the molecular mechanisms of arsenic (As)-associated carcinogenesis, we performed proteomic analysis on E7 immortalized human uroepithelial cells after treatment with As in vitro. Quantitative proteomics was performed using stable isotope dimethyl labeling coupled with two-dimensional liquid chromatography peptide separation and mass spectrometry (MS)/MS analysis. Among 285 proteins, a total of 26 proteins were upregulated (ratio > 2.0) and 18 proteins were downregulated (ratio < 0.65) by As treatment, which are related to nucleotide binding, lipid metabolism, protein folding, protein biosynthesis, transcription, DNA repair, cell cycle control, and signal transduction. This study reports the potential significance of nucleophosmin (NPM) in the As-related bladder carcinogenesis. NPM was universally expressed in all of uroepithelial cell lines examined, implying that NPM may play a role in human bladder carcinogenesis. Upregulation of NPM tends to be dose- and time-dependent after As treatment. Expression of NPM was associated with cell proliferation, migration and anti-apoptosis. On the contrary, soy isoflavones inhibited the expression of NPM in vitro. The results suggest that NPM may play a role in the As-related bladder carcinogenesis, and soybean-based foods may have potential in the suppression of As/NPM-related tumorigenesis.

• OSTI ID: 21344833
• Journal Information: Toxicology and Applied Pharmacology, Vol. 242, Issue 2; Other Information: DOI: 10.1016/j.taap.2009.09.016; PII: S0041-008X(09)00408-6; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ARSENIC
BIOSYNTHESIS
BLADDER
CARCINOGENESIS
CELL CYCLE
CELL PROLIFERATION
DNA REPAIR
DOSES
IN VITRO
LABELLED COMPOUNDS
LIPIDS
LIQUID COLUMN CHROMATOGRAPHY
MASS SPECTROSCOPY
MEN
METABOLISM
NUCLEOTIDES
PEPTIDES
SOYBEANS
STABLE ISOTOPES
TIME DEPENDENCE
TRANSCRIPTION
ANIMALS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CHROMATOGRAPHY
ELEMENTS
FOOD
ISOTOPES
MALES
MAMMALS
MAN
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PLANTS
PRIMATES
PROTEINS
REPAIR
SEEDS
SEMIMETALS
SEPARATION PROCESSES
SPECTROSCOPY
SYNTHESIS
URINARY TRACT
VEGETABLES
VERTEBRATES