Identification of novel proteins associated with the development of chemoresistance in malignant melanoma using two-dimensional electrophoresis.
A model system for studying chemoresistance in human melanoma cells (MeWo) has been established utilizing the four commonly used cytotoxic drugs vindesine, cisplatin, fotemustine and etoposide to yield stable drug-resistant sublines. We analyzed phenotypical differences between MeWo cells and their chemoresistant counterparts using two-dimensional electrophoresis. Proteins that were overexpressed in chemoresistant cell lines were purified and identified using matrix assisted laser desorption/ionization-time of flight - mass spectrometry (MALDI-TOF-MS) and microsequencing. Here we show that four proteins, namely the translationally controlled tumor protein, the human elongation factor 1-delta, tetratricopeptide repeat protein and the isoform 14-3-3-gamma of the 14-3-3-family are overexpressed in chemoresistant melanoma cell lines. The significance of these findings is now being verified using transfection experiments with the aim of developing more effective chemotherapy protocols.
Sinha
P
P
Institut für Laboratoriums-medizin und Pathobiochemie, Universitätsklinikum Charité, Medizinische Fakultät der Humboldt Universität zu Berlin, Germany.
Kohl
S
S
Fischer
J
J
Hütter
G
G
Kern
M
M
Köttgen
E
E
Dietel
M
M
Lage
H
H
Schnölzer
M
M
Schadendorf
D
D
D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins