Identification of proteins differentially expressed in adriamycin-resistant (pumc-91/ADM) and parental (pumc-91) human bladder cancer cell lines by proteome analysis

J Cancer Res Clin Oncol. 2013 Mar;139(3):509-19. doi: 10.1007/s00432-012-1350-8. Epub 2012 Nov 27.

Abstract

Purpose: Resistance to chemotherapy drugs remains a difficult problem in bladder cancer treatment. Protein expression is an important factor underlying multidrug resistance (MDR) in bladder cancer. The aim of the study was to explore differentially expressed proteins responsible for MDR between an adriamycin-resistant human bladder cancer cell line (pumc-91/ADM) and its parental cell line (pumc-91).

Methods: Two-dimensional gel electrophoresis (2-DE) combining image analysis was used to screen the differentially expressed protein spots between the pumc-91/ADM and pumc-91 cell lines. Then, the protein spots were identified using MALDI-TOF/TOF mass spectrometry. Among the identified proteins, annexin A2 (ANXA2) and nucleophosmin (NPM1) were then further verified using RT-PCR and Western blot analysis.

Results: A total of 30 proteins, including 19 up-regulated and 11 down-regulated proteins, were successfully identified in pumc-91/ADM. According to their different functions, these 30 proteins were classified into 12 categories. Annexin A2 (ANXA2) and nucleophosmin (NPM1) were up-regulated in pumc-91/ADM compared with pumc-91.

Conclusion: The proteins identified may have an important clinical significance in MDR, and ANXA2 and NPM1 may take part in mechanism of MDR in bladder cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibiotics, Antineoplastic / therapeutic use
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Doxorubicin / therapeutic use*
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Molecular Sequence Data
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / metabolism
  • Nucleophosmin
  • Proteome / analysis*
  • Proteome / metabolism
  • Proteomics / methods
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology
  • Validation Studies as Topic

Substances

  • Antibiotics, Antineoplastic
  • NPM1 protein, human
  • Neoplasm Proteins
  • Proteome
  • Nucleophosmin
  • Doxorubicin