title: Differentially expressed proteins in human MCF-7 breast cancer cells sensitive and resistant to paclitaxel.
abstract: Resistance of cancer cells to chemotherapeutic agents is one of the main causes of treatment failure. In order to detect proteins potentially involved in the mechanism of resistance to taxanes, we assessed differences in protein expression in MCF-7 breast cancer cells that are sensitive to paclitaxel and in the same cells with acquired resistance to paclitaxel (established in our lab). Proteins were separated using two-dimensional electrophoresis. Changes in their expression were determined and proteins with altered expression were identified using mass spectrometry. Changes in their expression were confirmed using western blot analysis. With these techniques, we found three proteins expressed differently in resistant MCF-7 cells, i.e., thyroid hormone-interacting protein 6 (TRIP6; upregulated to 650%), heat shock protein 27 (HSP27; downregulated to 50%) and cathepsin D (downregulated to 28%). Silencing of TRIP6 expression by specific siRNA leads to decreased number of grown resistant MCF-7 cells. In the present study we have pointed at some new directions in the studies of the mechanism of resistance to paclitaxel in breast cancer cells.
authors.affiliation: Department of Cell & Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: nela.pavlikova@lf3.cuni.cz.
authors.forename: Nela
authors.initials: N
authors.lastname: Pavlíková
authors.affiliation: Department of Cell & Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Irena
authors.initials: I
authors.lastname: Bartoňová
authors.affiliation: Department of Cell & Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Kamila
authors.initials: K
authors.lastname: Balušíková
authors.affiliation: Department of Cell & Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: Dana.Kopperova@seznam.cz.
authors.forename: Dana
authors.initials: D
authors.lastname: Kopperova
authors.affiliation: Laboratory of Molecular Structure Characterization, Institute of Microbiology,v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Halada
authors.affiliation: Department of Cell & Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Kovář
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms; D002402:Cathepsin D / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D060588:LIM Domain Proteins / Q000378:metabolism; D061986:MCF-7 Cells; D018832:Molecular Chaperones; D017239:Paclitaxel / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex; D020543:Proteome / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000972:Antineoplastic Agents, Phytogenic; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D060588:LIM Domain Proteins; D018832:Molecular Chaperones; C092282:PSMC5 protein, human; D020543:Proteome; D014157:Transcription Factors; C533922:CTSD protein, human; D002402:Cathepsin D; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities; D017239:Paclitaxel
keywords: 2-D electrophoresis; Breast cancer; Cathepsin D; Heat shock protein 27; TRIP6; Taxane resistance