Chromosomal imbalances associated with drug resistance and thermoresistance in human pancreatic carcinoma cells

Authors: Holger Tönnies¹; Hermann Lage²

Source: European Journal of Cell Biology, Volume 83, Number 10, October 2004 , pp. 591-601(11)

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Abstract:

Resistance to therapeutic treatment is the major obstacle to advances in the successful management of pancreatic cancer. To characterize chromosomal alterations associated with different phenotypes of acquired multidrug resistance (MDR) and thermoresistance, comparative genomic hybridization (CGH) was applied to compare human pancreatic carcinoma-derived cells. This panel of cell lines consists of the parental, drug- and thermosensitive pancreatic carcinoma cell line EPP85 – 181P, its atypical MDR variant EPP85 – 181RNOV, the classical MDR subline EPP85 – 181RDB, and their thermoresistant counterparts EPP85 – 181P-TR, EPP85 – 181RNOV-TR, and EPP85 – 181RDB-TR, respectively. CGH using 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 23 members of the family of ABC transporters, 27 members of the family of cytochrome P450 (CYP) monooxygenases, various molecular chaperones, DNA repair enzymes, and factors involved in the regulation of cell cycle and apoptosis. The importance of these cell variant-specific genomic imbalances in the development of MDR and thermoresistance is discussed and remains to be elucidated.

Document Type: Research article

DOI: http://dx.doi.org/10.1078/0171-9335-00414

Affiliations: 1: Institute of Human Genetics, Humboldt University Berlin, Charité Campus Virchow-Klinikum, Berlin, Germany 2: Institute of Pathology, Humboldt University Berlin, Charité Campus Mitte, Berlin, Germany

Publication date: 2004-10-01