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Epigenetic silencing of S100A2 in bladder and head and neck cancers

Juna Lee1, Piotr T Wysocki2, Ozlem Topaloglu2

  • 1Graduate Program in Human Genetics and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Oncoscience
|June 23, 2015
PubMed

Insights

The S100A2 gene, a potential tumor suppressor, is frequently silenced by promoter methylation in head and neck and bladder cancers. This methylation is detectable in urine and linked to tumor progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • S100A2 is a member of the S100 protein family.
  • S100A2 is known to be downregulated in various human cancers, suggesting a tumor suppressor role.

Purpose of the Study:

  • To investigate the expression and methylation status of S100A2 in head and neck and bladder cancers.
  • To elucidate the mechanism behind S100A2 downregulation.

Main Methods:

  • Assessed S100A2 mRNA and protein expression in cancer cell lines.
  • Utilized 5-aza-2'-deoxycytidine treatment to study methylation reversibility.
  • Analyzed S100A2 promoter methylation in primary tumor tissues and urine samples.
  • Correlated methylation levels with tumor progression.

Main Results:

  • Reduced S100A2 expression was observed in head and neck and bladder cancer cell lines.
  • S100A2 silencing is associated with aberrant promoter methylation, reversible with 5-aza-2'-deoxycytidine.
  • High frequency of S100A2 promoter methylation in primary head and neck (90%) and bladder (80%) cancers compared to normal tissues.
  • S100A2 methylation is detectable in urine, more prevalent in bladder cancer patients (96%) than healthy individuals (48%).
  • Increased S100A2 methylation correlates with bladder cancer progression (p<0.01).

Conclusions:

  • Methylation-associated inactivation of S100A2 is a frequent event in head and neck and bladder cancer tumorigenesis.
  • S100A2 promoter methylation serves as a potential biomarker for bladder cancer detection in urine.
  • S100A2 inactivation may play a significant role in the development and progression of these cancers.
Keywords:
S100A2bladder cancerepigeneticshead and neck cancermethylation

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