Epigenetic silencing of S100A2 in bladder and head and neck cancers

Juna Lee1, Piotr T. Wysocki2, Ozlem Topaloglu2, Leonel Maldonado2, Mariana Brait2, Shahnaz Begum5, David Moon2, Myoung Sook Kim2, Joseph A. Califano2,6, David Sidransky2,3, Mohammad O. Hoque2,3,4 and Chulso Moon1,2,3

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

2 Department of Otolaryngology – Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

3 Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

4 Department of Urology, Johns Hopkins University, Baltimore, Maryland, USA

5 Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA

6 Milton J. Dance Head and Neck Center. Greater Baltimore Medical Center, Baltimore, Maryland, USA


Chulso Moon, email:

Mohammad Obaidul Hoque, email:

Keywords: S100A2, methylation, head and neck cancer, bladder cancer, epigenetics

Received: January 29, 2015 Accepted: March 04, 2015 Published: March 16, 2015


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 methylation-associated inactivation of S100A2 is frequent and may be an important event in the tumorigenesis of head&neck and bladder cancer.

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