Abstracts (poster) - Wissenschaft Online

OLUSOLA DOKUN, WOLFGANG SCHULZ
DNA hypomethylation of SNCG (synuclein-gamma) in cancer:
tumor-specific or cell type- specific?
SNCG is one of few single-copy genes reported to be activated by DNA hypomethylation
in human cancers. Accordingly, a microarray comparison of cultured urothelial carcinoma
(UC) and normal cells from the same patient indicated a 5-fold upregulation. Of 13 UC
cell lines, 6 showed overexpression, but 7 very low levels vs. normal cells. Similarly, in
indivdiual carcinoma tissues, both increased and strongly diminished SNCG expressions
were found. Treatment with the DNA methyltransferase inhibitor 5-aza-2-deoxycytidine
induced expression in non-expressing cell lines. Bisulfite sequencing revealed dense
methylation of the SNCG promoter in UC lines without expression, whereas normal
urothelial cells and expressing UC lines lacked methylation. Investigation of a larger
range of cells showed partial methylation of SNCG in fibroblasts, blood leukocytes and
ureteral connective tissue. In fibroblasts low expression was found. The promoter was
unmethylated in normal prostate epithelial cells, but densely methylated in prostate
cancer cell lines. These data demonstrate cell type-specific methylation of the SNCG
promoter, i.e. low methylation in epithelia and partial methylation in connective tissue
and blood. In carcinomas, downregulation of SNCG appears associated with
hypermethylation, whereas upregulation occurs in cells with an already unmethylated
promoter and not by hypomethylation. We propose SNCG as a new example of a gene
subject to tissue-specific methylation.
Literature
Hoffmann MJ, Schulz WA. 2005. Causes and consequences of DNA Hypomethylation in
human cancer. Biochem cell bio. 83:296-321.
•Liu H, Liu W, Wu Y, Zhou Y, Xue R, Luo C, Wang L, Zhao W, Jiang JD, Liu J. 2005. Loss
of epigenetic control of synuclein-gamma gene as a molecular indicator of metastasis in
a wide range of human cancers. Cancer Res 65:7635-7643.
contact:
MR OLUSOLA DOKUN
HEINRICH HEINE UNIVERSITY
DEPT. OF UROLOGY
olusolayakub.dokun@uni-duesseldorf.de
UNIVERSITATSTR. 1
40225 DUESSELDORF (GERMANY)