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Specific-site methylation of tumour suppressor ANKRD11 in breast cancer

Sue Ping Lim1, Nick C Wong, Rachel J Suetani

  • 1Cancer Therapeutics Laboratory, Discipline of Medicine, The University of Adelaide, South Australia, Australia. sue.lim@adelaide.edu.au

European Journal of Cancer (Oxford, England : 1990)
|April 28, 2012
PubMed

Insights

ANKRD11 acts as a tumor suppressor in breast cancer. Aberrant DNA methylation in a specific promoter region of ANKRD11 correlates with its down-regulation and contributes to breast tumor development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • The ANKRD11 gene is implicated as a tumor suppressor in breast cancer.
  • ANKRD11 functions as a co-activator of p53, a critical protein in cancer suppression.
  • Down-regulation of ANKRD11 is observed in association with breast tumorigenesis.

Purpose of the Study:

  • To investigate the role of DNA methylation in the down-regulation of ANKRD11 in breast cancer.
  • To identify specific regions within the ANKRD11 promoter susceptible to methylation.
  • To elucidate the mechanism by which ANKRD11's tumor suppressor function is affected in breast cancer.

Main Methods:

  • Utilized DNA demethylating agents to observe ANKRD11 expression changes in breast cancer cell lines.
  • Employed dual-luciferase reporter assays to assess the transcriptional activity of the ANKRD11 promoter region.
  • Analyzed DNA methylation patterns using the SEQUENOM Epityper Platform in breast tumors and normal tissues.

Main Results:

  • Up-regulation of ANKRD11 expression was observed upon treatment with DNA demethylating agents.
  • A CpG-rich region (-661 to -571 bp) upstream of the ANKRD11 transcription start site demonstrated significant transcriptional activity.
  • Frequent methylation was detected in the -770 to -323 bp region of the ANKRD11 promoter in breast tumors.
  • A specific 19 bp region containing three CpG sites showed significantly higher methylation levels (40%) in tumors compared to normal samples (6%).

Conclusions:

  • The findings support the role of ANKRD11 as a tumor suppressor gene in breast cancer.
  • Aberrant DNA methylation of three CpG sites within a 19 bp region of the ANKRD11 promoter is likely responsible for its down-regulation.
  • This epigenetic alteration contributes to the development of breast cancer.

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