Identification of Genes with Differential Expression in Acquired Drug-Resistant Gastric Cancer Cells Using High-Density Oligonucleotide Microarrays
Purpose: A major obstacle in chemotherapy is treatment failure due to anticancer drug resistance. The emergence of acquired resistance results from host factors and genetic or epigenetic changes in the cancer cells. The purpose of this study was to identify differentially expressed genes associated...
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Published in | Clinical cancer research Vol. 10; no. 1; pp. 272 - 284 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
01.01.2004
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Subjects | |
Online Access | Get full text |
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Summary: | Purpose: A major obstacle in chemotherapy is treatment failure due to anticancer drug resistance. The emergence of acquired resistance
results from host factors and genetic or epigenetic changes in the cancer cells. The purpose of this study was to identify
differentially expressed genes associated with acquisition of resistance in human gastric cancer cells.
Experimental Design: We performed global gene expression analysis in the acquired drug-resistant gastric cancer cell lines to the commonly used
drugs 5-fluorouracil, doxorubicin, and cisplatin using Affymetrix HG-U133A microarray. The gene expression patterns of 10
chemoresistant gastric cancer cell lines were compared with those of four parent cell lines using fold-change and Wilcoxon’s
test for data analysis.
Results: We identified over 250 genes differentially expressed in 5-fluorouracil-, cisplatin-, or doxorubicin-resistant gastric cancer
cell lines. Our expression analysis also identified eight multidrug resistance candidate genes that were associated with resistance
to two or more of the tested chemotherapeutic agents. Among these, midkine ( MDK ), a heparin-binding growth factor, was overexpressed in all drug-resistant cell lines, strongly suggesting that MDK might contribute to multidrug resistance in gastric cancer cells.
Conclusions: Our investigation provides comprehensive gene information associated with acquired resistance to anticancer drugs in gastric
cancer cells and a basis for additional functional studies. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-1025-3 |