Upregulation of stem cell genes in multidrug resistant K562 leukemia cells.
The transmembrane transporter P-glycoprotein (P-gp) encoded by ABCB1, is one major cause for multidrug resistance (MDR). We compared the genomic profile and gene expression pattern of the P-gp positive K562VCR cells with parental P-gp negative K562wt cells. In K562VCR array CGH revealed amplification of ABCB1, ABCB4, ABCB5 and SEMA3D, whereas expression microarrays demonstrated upregulation of stem cell genes (e.g. KIT and HOXB4), anti-apoptotic genes (e.g. IGF1R and CCNG1), and downregulation of pro-apoptotic genes (e.g. CASP4, 6 and 7). Thus, K562VCR cells disclose stem cell characteristics including a range of drug resistance mechanisms possibly attained as a stem cell program switched on en bloc.
Lehne
Gustav
G
Department of Clinical Pharmacology, Oslo University Hospital Rikshospitalet, Norway. gustav.lehne@medisin.uio.no
Grasmo-Wendler
Unn-Hilde
UH
Berner
Jeanne-Marie
JM
Meza-Zepeda
Leonardo A
LA
Adamsen
Birgitte Lid
BL
Flack
Aksel
A
Reiner
Andrew
A
Clausen
Ole Petter Fraas
OP
Hovig
Eivind
E
Myklebost
Ola
O
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D020014:K562 Cells / Q000473:pathology*; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D019089:Stem Cell Factor / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation
C513055:ABCB1 protein, human; C480744:ABCB5 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D019089:Stem Cell Factor; D014157:Transcription Factors; C095122:multidrug resistance protein 3