Nucleophosmin in the pathogenesis of arsenic-related bladder carcinogenesis revealed by quantitative proteomics.
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.
Chen
Shu-Hui
SH
Department of Chemistry, College of Sciences, National Cheng Kung University, Tainan 701, Taiwan.
Wang
Yi-Wen
YW
Hsu
Jue-Liang
JL
Chang
Hong-Yi
HY
Wang
Chi-Yun
CY
Shen
Po-Tsun
PT
Chiang
Chi-Wu
CW
Chuang
Jing-Jing
JJ
Tsai
Hung-Wen
HW
Gu
Po-Wen
PW
Chang
Fang-Chih
FC
Liu
Hsiao-Sheng
HS
Chow
Nan-Haw
NH
D001151:Arsenic / Q000633:toxicity*; D001483:Base Sequence; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D017931:DNA Primers; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction; D040901:Proteomics; D034622:RNA Interference; D053719:Tandem Mass Spectrometry; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
D002273:Carcinogens; D017931:DNA Primers; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D001151:Arsenic