Epigenetic silencing of S100A2 in bladder and head and neck cancers

Juna Lee, Piotr T. Wysocki, Ozlem Topaloglu, Leonel Maldonado, Mariana Brait, Shahnaz Begum, David Moon, Myoung Sook Kim, Joseph A. Califano, David Sidransky, Mohammad O. Hoque, Chulso Moon

Research output: Contribution to journalArticle

Abstract

S100A2, a member of the S100 protein family, is known to be downregulated in a number of human cancers, leading to its designation as a potential tumor suppressor gene. Here, we investigated the expression and methylation status of S100A2 in head&neck and bladder cancer. Reduced mRNA and protein expression was observed in 8 head&neck and bladder cancer cell lines. To explore the mechanism responsible for the downregulation of S100A2, we treated six cell lines with 5-aza-2'-deoxycytidine. We found S100A2 is silenced in association with aberrant promoter-region methylation and its expression is restored with 5-aza-2'-deoxycytidine treatment. Of 31 primary head&neck cancer cases and 31 bladder cancer cases, promoter methylation was detected in 90% and 80% of cases, respectively. Interestingly, only 1/9 of normal head&neck tissues and 2/6 of normal bladder tissues showed promoter methylation. S100A2 promoter methylation can be detected in urine and is more frequent in bladder cancer patients than in healthy subjects (96% vs 48% respectively). Moreover, increased methylation of S100A2 is linked to the progression of the tumor in bladder cancer (p < 0.01). Together, this data shows that methylationassociated inactivation of S100A2 is frequent and may be an important event in the tumorigenesis of head&neck and bladder cancer.

Original languageEnglish (US)
Pages (from-to)410-418
Number of pages9
JournalOncoscience
Volume2
Issue number4
DOIs
StatePublished - Jan 1 2015

Keywords

  • Bladder cancer
  • Epigenetics
  • Head and neck cancer
  • Methylation
  • S100A2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Lee, J., Wysocki, P. T., Topaloglu, O., Maldonado, L., Brait, M., Begum, S., Moon, D., Kim, M. S., Califano, J. A., Sidransky, D., Hoque, M. O., & Moon, C. (2015). Epigenetic silencing of S100A2 in bladder and head and neck cancers. Oncoscience, 2(4), 410-418. https://doi.org/10.18632/oncoscience.140