The multidrug resistance phenotype (MDR) is one of the major causes of failure in cancer chemotherapy and it is associated with the over-expression of P-glycoprotein (P-gp or MDR1) in tumor cell membranes. A constitutive NF-kappaB activity has been observed in several haematological malignancies and
Upregulation of stem cell genes in multidrug resistant K562 leukemia cells
β Scribed by Gustav Lehne; Unn-Hilde Grasmo-Wendler; Jeanne-Marie Berner; Leonardo A. Meza-Zepeda; Birgitte Lid Adamsen; Aksel Flack; Andrew Reiner; Ole Petter Fraas Clausen; Eivind Hovig; Ola Myklebost
- Publisher
- Elsevier Science
- Year
- 2009
- Tongue
- English
- Weight
- 828 KB
- Volume
- 33
- Category
- Article
- ISSN
- 0145-2126
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β¦ Synopsis
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.
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