Specific-site methylation of tumour suppressor ANKRD11 in breast cancer

Lim, Sue Ping, Wong, Nick C., Suetani, Rachel J., Ho, Kristen, Ng, Jane Lee, Neilsen, Paul M., Gill, Peter G., Kumar, Raman and Callen, David F. (2012) Specific-site methylation of tumour suppressor ANKRD11 in breast cancer. European Journal of Cancer, 48 17: 3300-3309. doi:10.1016/j.ejca.2012.03.023

Author Lim, Sue Ping
Wong, Nick C.
Suetani, Rachel J.
Ho, Kristen
Ng, Jane Lee
Neilsen, Paul M.
Gill, Peter G.
Kumar, Raman
Callen, David F.
Title Specific-site methylation of tumour suppressor ANKRD11 in breast cancer
Journal name European Journal of Cancer   Check publisher's open access policy
ISSN 0959-8049
Publication date 2012-11-01
Sub-type Article (original research)
DOI 10.1016/j.ejca.2012.03.023
Open Access Status Not Open Access
Volume 48
Issue 17
Start page 3300
End page 3309
Total pages 10
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon Press
Language eng
Abstract ANKRD11 is a putative tumour suppressor gene in breast cancer, which has been shown in our laboratory to be a co-activator of p53. Our data suggest that down-regulation of ANKRD11 is associated with breast tumourigenesis. Breast cancer cell lines treated with DNA demethylating agents resulted in up-regulation of ANKRD11 expression suggesting that promoter DNA methylation may be responsible for its down-regulation. The transcriptional activity of a CpG-rich region 2 kb upstream of the transcription initiation site of ANKRD11 was investigated using dual-luciferase reporter assays. The constructs carrying -661 to -571 bp promoter sequence showed significant transcriptional activity. Using the SEQUENOM Epityper Platform, the region between -770 and +399 bp was analysed in 25 breast tumours, four normal breast tissues and five normal blood samples. The region between -770 and -323 bp was shown to be frequently methylated in breast tumours. The methylation patterns of all analysed CpGs in this region were identical in the normal and tumour samples, except for a 19 bp region containing three CpG sites. These sites had significantly higher levels of methylation in tumours (40%) compared to normal samples (6%). Our findings support the role of ANKRD11 as a tumour suppressor gene and suggest that aberrant DNA methylation of three CpGs in a 19 bp region within the ANKRD11 promoter may be responsible for its down-regulation in breast cancer.
Keyword ANKRD11
Breast cancer
Promoter activity
Specific DNA methylation
Tumour suppressor
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 30 Nov 2015, 21:50:03 EST by Rachel Suetani on behalf of Queensland Brain Institute