Searching cell-secreted proteomes for potential urinary bladder tumor markers.
To search for biomarkers critical for bladder carcinoma diagnosis and prognosis, secreted proteomes of highly malignant U1 and pre-malignant U4 cell lines were initially analyzed. Proteins in the culture media of the U1 and U4 cell lines were systematically examined by SDS-PAGE combined with MALDI-TOF MS. Among them, expression of pro-u-plasminogen activator (pro-u-PA) was confirmed by Western blot analysis and further evaluated. In analyzing urine samples from bladder cancer patients and normal subjects, we established a statistically significant relationship between the low level and absence of pro-u-PA in urine with high stages and grades of the tumor samples. Constitutive expression of Ras dominant negative protein led to increased expression of pro-u-PA in culture media, indicating that the loss of pro-u-PA is associated with oncogenic transformation. Analysis of cancer-secreted proteomes can be a feasible, non-invasive and efficient strategy for searching potential bladder tumor biomarkers. Our work also has identified the loss of pro-u-PA in urine as potential marker of more advanced bladder carcinoma.
Lin
Chiao-Yun
CY
Department of Pharmacology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan, ROC.
Tsui
Ke-Hung
KH
Yu
Chih-Chia
CC
Yeh
Chun-Wei
CW
Chang
Phei-Lang
PL
Yung
Benjamin Yat-Ming
BY
D014408:Biomarkers, Tumor / Q000378:metabolism* / Q000652:urine; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D006801:Humans; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000652:urine; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000378:metabolism / Q000652:urine
D014408:Biomarkers, Tumor; D020543:Proteome; D014568:Urokinase-Type Plasminogen Activator