PMID: 9661702Jul 14, 1998Paper

Demethylation of the human MDR1 5' region accompanies activation of P-glycoprotein expression in a HL60 multidrug resistant subline

Somatic Cell and Molecular Genetics
L DesideratoA A Piper

Abstract

Chemotherapy is frequently limited by the development of multidrug resistance, a major cause of which is activation of the P-glycoprotein-encoding MDR1 gene. We have previously developed a P-glycoprotein-expressing multidrug resistant subline (HL60/E8) from the non-P-glycoprotein-expressing human HL60 promyelocytic leukemia cell line. A possible cause of MDR1 silencing in HL60 cells is methylation of the promoter proximal region, thus demethylation occurring as a result of drug treatment may be responsible for MDR1 activation in the multidrug resistant subline. Using the bisulphite genomic sequencing technique we demonstrated that HL60 DNA is methylated at multiple sites within two distinct areas, one upstream and one downstream of the transcription start point. Only a single site in each area was methylated in all strands examined, with the remaining adjacent sites showing partial methylation. In contrast, DNA from the multidrug resistant HL60/E8 subline was unmethylated at essentially all sites in both areas. Thus the development of the P-glycoprotein-expressing multidrug resistant subline was associated with demethylation of the MDR1 5' region.

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Citations

Oct 22, 2003·Experimental Cell Research·Emma K Baker, Assam El-Osta
Oct 31, 2003·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Manel Esteller
Feb 22, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kevin G Chen, Branimir I Sikic
Aug 9, 2006·Journal of Translational Medicine·Blanca Segura-PachecoAlfonso Duenas-González
Aug 27, 2014·American Journal of Veterinary Research·Hirotaka TomiyasuHajime Tsujimoto
May 4, 2004·Cancer Genetics and Cytogenetics·Xiaoming YaoAndrew R Hoffman
May 15, 2002·Biochimica Et Biophysica Acta·Jidong ShanHao-peng Xu
Nov 19, 2013·PloS One·Simona Delle MonacheRosella Cardigno Colonna
Oct 18, 2020·Cells·Katja Zappe, Margit Cichna-Markl
Aug 11, 2001·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Phillip KantharidisJohn Zalcberg

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