Association of genomic imbalances with drug resistance and thermoresistance in human gastric carcinoma cells.
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.
Tönnies
Holger
H
Institute of Human Genetics, Humboldt University Berlin, Charité Campus Virchow-Klinikum, Berlin, Germany.
Poland
Julia
J
Sinha
Pranav
P
Lage
Hermann
H
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
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