title: Differentially expressed genes associated with cisplatin resistance in human ovarian adenocarcinoma cell line A2780.
abstract: Ovarian cancer cells are usually initially sensitive to platinum-based chemotherapy, such as cisplatin (CDDP), but typically become resistant over time. Such drug resistance is a serious impediment to successful disease treatment, and the molecular mechanisms responsible for resistance are not fully understood. In search of novel mechanisms that may lead to the development of CDDP chemoresistance, we used subtractive hybridization to identify differentially expressed genes in CDDP resistant CP70 and C200 cells vs. CDDP sensitive A2780 human ovarian adenocarcinoma cells. We analyzed 256 randomly selected clones. Subtraction efficiency was determined by dot blot and DNA sequencing. Confirmation of differentially expressed cDNAs was done by virtual northern blot analysis, and 17 genes that were differentially expressed in CDDP resistant cell lines vs. CDDP sensitive A2780 cells were identified. The expression of 10 of these genes was low or undetectable in sensitive A2780 cells in comparison to resistant cells and an additional seven genes were more highly expressed in resistant CP70 and C200 vs. A2780 cells. Our identified genes are involved in numerous and diverse cellular processes, such as inhibition of apoptosis (ARHGDIB), stress response (HSPCA, TRA1), chromatin condensation (CNAP1, RanBP2), invasiveness of cells (MMP10), alteration of Ca(2+) homeostasis (ASPH, ATP2B1) and others. Further characterization of these genes and gene products should yield important insights into the biology of CDDP resistance in ovarian carcinoma.
authors.affiliation: Laboratory for Cell Biology, Institute of Biology & Ecology, P.J. Šafárik University, Košice, Slovak Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Solár
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Sytkowski
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D015152:Blotting, Northern; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D053506:Matrix Metalloproteinase 10 / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D006899:Mixed Function Oxygenases / Q000235:genetics; D018832:Molecular Chaperones / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D028861:Nuclear Pore Complex Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins
chemical_list: C506952:ATP2B1 protein, human; D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009124:Muscle Proteins; C413383:NCAPD2 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C053387:endoplasmin; C094493:ran-binding protein 2; D006899:Mixed Function Oxygenases; C419389:ASPH protein, human; D053506:Matrix Metalloproteinase 10; D053499:Plasma Membrane Calcium-Transporting ATPases; D002945:Cisplatin