Imperial College London
Alternate

DrNatalieShenker

Faculty of Medicine, Department of Surgery & Cancer

Research Fellow
 
 
 
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Contact

 

natalie.shenker

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Shenker:2015:10.1186/s12885-015-1335-5,
author = {Shenker, NS and Flower, KJ and Wilhelm-Benartzi, CS and Dai, W and Bell, E and Gore, E and El, Bahrawy M and Weaver, G and Brown, R and Flanagan, JM},
doi = {10.1186/s12885-015-1335-5},
journal = {BMC Cancer},
pages = {337--337},
title = {Transcriptional implications of intragenic DNA methylation in the oestrogen receptor alpha gene in breast cancer cells and tissues.},
url = {http://dx.doi.org/10.1186/s12885-015-1335-5},
volume = {15},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: DNA methylation variability regions (MVRs) across the oestrogen receptor alpha (ESR1) gene have been identified in peripheral blood cells from breast cancer patients and healthy individuals. In contrast to promoter methylation, gene body methylation may be important in maintaining active transcription. This study aimed to assess MVRs in ESR1 in breast cancer cell lines, tumour biopsies and exfoliated epithelial cells from expressed breast milk (EBM), to determine their significance for ESR1 transcription. METHODS: DNA methylation levels in eight MVRs across ESR1 were assessed by pyrosequencing bisulphite-converted DNA from three oestrogen receptor (ER)-positive and three ER-negative breast cancer cell lines. DNA methylation and expression were assessed following treatment with DAC (1 μM), or DMSO (controls). ESR1 methylation levels were also assayed in DNA from 155 invasive ductal carcinoma biopsies provided by the Breast Cancer Campaign Tissue Bank, and validated with DNA methylation profiles from the TCGA breast tumours (n = 356 ER-pos, n = 109 ER-neg). DNA methylation was profiled in exfoliated breast epithelial cells from EBM using the Illumina 450 K (n = 36) and pyrosequencing in a further 53 donor samples. ESR1 mRNA levels were measured by qRT-PCR. RESULTS: We show that ER-positive cell lines had unmethylated ESR1 promoter regions and highly methylated intragenic regions (median, 80.45%) while ER-negative cells had methylated promoters and lower intragenic methylation levels (median, 38.62%). DAC treatment increased ESR1 expression in ER-negative cells, but significantly reduced methylation and expression of ESR1 in ER-positive cells. The ESR1 promoter was unmethylated in breast tumour biopsies with high levels of intragenic methylation, independent of ER status. However, ESR1 methylation in the strongly ER-positive EBM DNA samples were very similar to ER-positive tumour cell lines. CONCLUSION:
AU  - Shenker,NS
AU  - Flower,KJ
AU  - Wilhelm-Benartzi,CS
AU  - Dai,W
AU  - Bell,E
AU  - Gore,E
AU  - El,Bahrawy M
AU  - Weaver,G
AU  - Brown,R
AU  - Flanagan,JM
DO  - 10.1186/s12885-015-1335-5
EP  - 337
PY  - 2015///
SN  - 1471-2407
SP  - 337
TI  - Transcriptional implications of intragenic DNA methylation in the oestrogen receptor alpha gene in breast cancer cells and tissues.
T2  - BMC Cancer
UR  - http://dx.doi.org/10.1186/s12885-015-1335-5
UR  - http://hdl.handle.net/10044/1/22182
VL  - 15
ER  -
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