Previous studies have suggested an important role of ERs (oestrogen receptors) in the pathogenesis of leukaemias. However, there is no information so far about the epigenetic characteristics of ERα isoforms and ERβ in leukaemias. In the present study, the mRNA expression and promoter CpG methylation of ERα isoforms (i.e. ERα-A, -B and -C) and ERβ in leukaemia cell lines were evaluated using RT–PCR (reverse transcription–PCR) and MSP (methylation-specific PCR) respectively. The methylation of ERs was further analysed in acute leukaemia patients by MSP and direct DNA sequencing. Although all ERα isoforms and ERβ were methylated in all leukaemia cell lines, except for ERα-C, which was unmethylated in HL-60 and K562 cell lines, only the expression of ERα-A was deficient in all cell lines and its expression could be reactivated by DNA demethylation reagents. With regard to the methylation characteristics in acute leukaemia patients, only ERα-A was inactivated and specifically methylated (95%; 38/40) in almost all patients and unmethylated in all healthy controls, whereas ERα-B, -C and ERβ were methylated in both patients and healthy controls. This result suggested that the methylated status of ERα-A might serve as an epigenetic biomarker of leukaemias. The present study is the first report that demonstrates selective inactivation of ERα isoforms through the promoter CpG methylation pathway in leukaemias.
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Research Article|
May 01 2009
Promoter CpG methylation of oestrogen receptors in leukaemia
Jie Yao;
Jie Yao
1
1Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, People's Republic of China
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Qing Huang;
Qing Huang
1
1Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, People's Republic of China
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Xiao-Bing Zhang;
Xiao-Bing Zhang
1Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, People's Republic of China
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Wei-Ling Fu
Wei-Ling Fu
2
1Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, People's Republic of China
2To whom correspondence should be addressed (email weilingfu@yahoo.com).
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Publisher: Portland Press Ltd
Received:
September 15 2008
Accepted:
September 22 2008
Accepted Manuscript online:
September 22 2008
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biosci Rep (2009) 29 (4): 211–216.
Article history
Received:
September 15 2008
Accepted:
September 22 2008
Accepted Manuscript online:
September 22 2008
Citation
Jie Yao, Qing Huang, Xiao-Bing Zhang, Wei-Ling Fu; Promoter CpG methylation of oestrogen receptors in leukaemia. Biosci Rep 1 August 2009; 29 (4): 211–216. doi: https://doi.org/10.1042/BSR20080140
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