Epigenetic silencing of S100A2 in bladder and head and neck cancers
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https://doi.org/10.18632/oncoscience.140
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
Correspondence:
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
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 methylation-associated inactivation of S100A2 is frequent and may be an important event in the tumorigenesis of head&neck and bladder cancer.
