Gene expression profiling in chemoresistant variants of three cell lines of different origin.
BACKGROUND
Drug resistance is a major problem in clinical cancer chemotherapy. Several mechanisms of resistance have been identified, but the underlying genomic changes are still poorly understood.


METHODS
Gene expression profiling, using cDNA microarray, was performed in eight cell lines (K562 leukemia, MCF-7 breast cancer and S1 colon cancer) with acquired resistance against five cytostatic drugs; daunorubicin (DNR), doxorubicin (DOX), vincristine (VCR), etoposide (VP) and mitoxantrone (MX).


RESULTS
The resistant cell lines clustered together based on their type of origin. Several genes encoding ABC transporters were highly up-regulated, most notably ABCB1 (MDR1) and ABCB4 in several cell lines and ABCG2 (MXR) specifically in MX-resistant cell lines. A pronounced down-regulation of several histones was noted in the MCF-7-derived resistant sublines. Altered expression was also seen in, e.g., GSTs, topoisomerases, caveolins, annexins and CD44.


CONCLUSIONS
These results will constitute a platform for further studies on specific pathways and biological processes involved in chemotherapy resistance.
Johnsson
Anders
A
Department of Oncology, University Hospital, S-221 85, Lund, Sweden. Anders.Johnsson@onk.lu.se
Vallon-Christensson
Johan
J
Strand
Carina
C
Litman
Thomas
T
Eriksen
Jens
J
D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis