title: The use of LC-MS to identify differentially expressed proteins in docetaxel-resistant prostate cancer cell lines.
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.
authors.affiliation: MTCI, National Institute for Cellular Biotechnology, DCU, Glasnevin, Dublin, Ireland. Kathleen.OConnell@dcu.ie
authors.forename: Kathleen
authors.initials: K
authors.lastname: O'Connell
authors.forename: Maria
authors.initials: M
authors.lastname: Prencipe
authors.forename: Amanda
authors.initials: A
authors.lastname: O'Neill
authors.forename: Claire
authors.initials: C
authors.lastname: Corcoran
authors.forename: Sweta
authors.initials: S
authors.lastname: Rani
authors.forename: Michael
authors.initials: M
authors.lastname: Henry
authors.forename: Paul
authors.initials: P
authors.lastname: Dowling
authors.forename: Paula
authors.initials: P
authors.lastname: Meleady
authors.forename: Lorraine
authors.initials: L
authors.lastname: O'Driscoll
authors.forename: William
authors.initials: W
authors.lastname: Watson
authors.forename: Robert
authors.initials: R
authors.lastname: O'Connor
mesh_terms: D045744:Cell Line, Tumor; D002853:Chromatography, Liquid / Q000379:methods; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D003598:Cytoskeletal Proteins; D011506:Proteins; D011838:Radiation-Sensitizing Agents; D011944:Receptors, Androgen; D043823:Taxoids; D000077143:Docetaxel