Journal Article

Promoter CpG hypermethylation and downregulation of DICE1 expression in prostate cancer

Seger, Jeannette, Wieacker, Peter F, Böhm, Malte, Buhtz, Peter, Wieland, Ilse, Allhoff, Ernst P, Röpke, Albrecht

2005

Overview

A critical region of loss of heterozygosity on human chromosome 13q14 harbors the tumor suppressor gene DICE1 ( DDX26 ). To elucidate the reduced DICE1 expression in tumor cells, the putative promoter sequence upstream of the DICE1 gene was analysed. This sequence shows a high GC content and is rich in CpG sites and binding sites of transcriptional factors. Promoter activity was identified within three overlapping fragments of the 800 bp sequence upstream of the DICE1 gene. A 13 bp deletion polymorphism detected in the DICE1 promoter region showed a decreased activity compared with the undeleted variant. However, this 13 bp deletion was seen in male control samples and patients with prostate cancer or benign prostatic hyperplasia at similar rates. A reduced DICE1 expression was observed in prostate cancer cell lines DU145 and LNCaP. This downregulation is associated with hypermethylation of the DICE1 promoter. Treatment of both prostate cancer cell lines with 5-azacytidine leads to upregulation of DICE1 expression. Hypermethylation of CpG sites of the DICE1 promoter was observed in four of eight analysed prostate cancers. This study suggests that transcriptional repression of DICE1 is caused by hypermethylation of the DICE1 promoter region in prostate cancer cells.

• Publisher: Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
• Subject: Apoptosis / Azacytidine / Base Sequence / Binding sites / Biological and medical sciences / Cell Biology / Cell physiology / Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes / Chromosome 13 / CpG Islands / DICE1 gene / DNA Methylation / DNA, Neoplasm - genetics / Down-Regulation / Fundamental and applied biological sciences. Psychology / Gene deletion / Gene polymorphism / Gene silencing / Genes / Heterozygosity / Human Genetics / Humans / Hyperplasia / Internal Medicine / Loss of Heterozygosity / Male / Medical sciences / Medicine / Medicine & Public Health / Molecular and cellular biology / Molecular genetics / Molecular Sequence Data / Nephrology. Urinary tract diseases / Oncology / original-paper / Polymorphism / Promoter Regions, Genetic / Prostate cancer / Prostatic Neoplasms - genetics / Ribosomal Proteins / RNA Helicases - genetics / Transcription factors / Transcription. Transcription factor. Splicing. Rna processing / Tumor cell lines / Tumor cells / Tumor suppressor genes / Tumor Suppressor Proteins - genetics / Tumors / Tumors of the urinary system / Urinary tract. Prostate gland