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A gene expression profile of tumor suppressor genes commonly methylated in bladder cancer.

Abstract：

PURPOSE:The functional relationship between promoter hypermethylation and gene inactivation has been demonstrated for few genes only. We examined the promoter methylation status of two important tumor suppressor genes APAF-1 and DAPK-1 in bladder cancer as well as the mRNA expression pattern of these two genes for possible correlation between promoter hypermethylation and transcriptional repression. METHODS:The methylation status and mRNA expression levels were related to clinicopathological features in 34 patients with transitional cell carcinoma (TCC) of the bladder with a median clinical follow-up of more than 45 months. Tissue from ten patients with nonmalignant disease served as a control group. Quantitative real-time PCR-based detection methods were used for determination of the normalized index of methylation (NIM) as well as the mRNA expression level. RESULTS:APAF-1 and DAPK-1 methylation and mRNA expression was observed in all tumor and normal control samples investigated. Methylation (NIM) levels were significantly higher in tumor tissue for APAF-1 and DAPK-1, but median mRNA expression levels did not differ significantly comparing tumorous and non tumorous tissue. No correlation between expression levels of APAF-1 and DAPK-1 mRNA and tumor stage or grade was observed. However, in superficial TCC a strong correlation between higher NIM levels and lower mRNA expression of the APAF-1 gene was observed (P = 0.014). CONCLUSIONS:Our results, although preliminary, provide first time in vivo expression analysis of the APAF-1 gene in bladder cancer specimen, suggesting expression control by promoter methylation in early stage tumor disease of the bladder.

journal_name

J Cancer Res Clin Oncol

journal_title

Journal of cancer research and clinical oncology

authors

Christoph F,Hinz S,Kempkensteffen C,Weikert S,Krause H,Schostak M,Schrader M,Miller K

doi

10.1007/s00432-006-0174-9

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

343-9

issue

6

eissn

0171-5216

issn

1432-1335

journal_volume

133

pub_type

杂志文章

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