The use of LC-MS to identify differentially expressed proteins in docetaxel-resistant prostate cancer cell lines

Proteomics. 2012 Jul;12(13):2115-26. doi: 10.1002/pmic.201100489.

Abstract

Docetaxel is a taxane-derived chemotherapy drug that has been approved for treatment of prostate cancer. While docetaxel is frequently used as a treatment for hormone-refractory prostate cancer, a subset of patients either do not respond to this treatment or those that do respond eventually become resistant to the drug over time. Resistance to docetaxel is complex and multi-factoral and further understanding of the cellular biochemistry underlying resistance is vital to improve treatment efficacy. To identify proteins altered in the resistant phenotype, three parental cell lines DU145, 22RV1 and PC-3, as well as their docetaxel resistant sub-lines, were subjected to quantitative label-free LC-MS proteomic profiling. A total of 189 significant (p < 0.05) protein abundance changes were identified in the DU145 resistant sub-lines, 254 in the 22RV1 sub-lines, and 51 and 72 in the 8 and 12 nM resistant PC-3 sub-lines, respectively. From these, 29 proteins demonstrated a significant (p < 0.05) fold change across two or more resistant variants. These included proteins indicative of an epithelial-to-mesenchemyl transition as well as altered heat shock response elements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chromatography, Liquid / methods
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Docetaxel
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mass Spectrometry / methods
  • Prostate / drug effects
  • Prostate / metabolism
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Proteins / genetics*
  • Proteins / metabolism
  • Proteomics / methods
  • Radiation-Sensitizing Agents / pharmacology*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Taxoids / pharmacology*

Substances

  • Cytoskeletal Proteins
  • Proteins
  • Radiation-Sensitizing Agents
  • Receptors, Androgen
  • Taxoids
  • Docetaxel