title: Association of genomic imbalances with drug resistance and thermoresistance in human gastric carcinoma cells.
abstract: Therapy resistance is the major obstacle to advances in successful cancer treatment. To characterize chromosomal alterations associated with different types of acquired MDR and thermoresistance, we applied CGH to compare a unique panel of human gastric carcinoma cells consisting of the parental, drug-sensitive and thermosensitive cancer cell line EPG85-257P, the atypical MDR variant EPG85-257RNOV, the classical MDR subline EPG85-257RDB and their thermoresistant counterparts EPG85-257P-TR, EPG85-257RNOV-TR and EPG85-257RDB-TR. CGH with genomic DNA prepared from these cell lines as probes successfully identified genomic gains and/or losses in chromosomal regions encoding putative genes associated with drug resistance and/or thermoresistance. These genes included various members of the families of ABC transporters and molecular chaperones. The importance of these cell variant-specific genomic imbalances in the development of MDR and thermoresistance is discussed and remains to be elucidated.
authors.affiliation: Institute of Human Genetics, Humboldt University Berlin, Charité Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Tönnies
authors.forename: Julia
authors.initials: J
authors.lastname: Poland
authors.forename: Pranav
authors.initials: P
authors.lastname: Sinha
authors.forename: Hermann
authors.initials: H
authors.lastname: Lage
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D002869:Chromosome Aberrations; D015342:DNA Probes; D003630:Daunorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005784:Gene Amplification; D017353:Gene Deletion; D005786:Gene Expression Regulation; D019450:Genes, MDR / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D008942:Mitoxantrone / Q000378:metabolism / Q000494:pharmacology; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D015342:DNA Probes; D018832:Molecular Chaperones; D008942:Mitoxantrone; D003630:Daunorubicin