title: Epigenetic silencing of S100A2 in bladder and head and neck cancers.
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.
authors.affiliation: Graduate Program in Human Genetics and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Juna
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Piotr T
authors.initials: PT
authors.lastname: Wysocki
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Topaloglu
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Leonel
authors.initials: L
authors.lastname: Maldonado
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Brait
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Begum
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Moon
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Myoung Sook
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA ; Milton J. Dance Head and Neck Center. Greater Baltimore Medical Center, Baltimore, Maryland, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA ; Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA ; Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA ; Department of Urology, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Mohammad O
authors.initials: MO
authors.lastname: Hoque
authors.affiliation: Graduate Program in Human Genetics and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA ; Department of Otolaryngology - Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA ; Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Chulso
authors.initials: C
authors.lastname: Moon
keywords: S100A2; bladder cancer; epigenetics; head and neck cancer; methylation