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Cancer Lett. 2012 Sep 28;322(2):177-84. doi: 10.1016/j.canlet.2012.03.001. Epub 2012 Mar 7.

Regulation of thrombomodulin expression in prostate cancer cells.

Author information

1
Institute of Clinical Chemistry and Laboratory Medicine, Technical University of Dresden, Medical Faculty "Carl Gustav Carus", Germany. Mario.Menschikowski@uniklinikum-dresden.de

Abstract

In carcinomas the expression of thrombomodulin (TM) is inversely correlated with tumour progression and metastasis. In the present study a decreased TM expression in human prostate cancer cell lines, LNCaP, DU-145, and PC-3, in relation to normal prostate epithelial cells (PrEC) is shown. Sequencing and methylation-specific high resolution melting (MS-HRM) analyses of bisulphite-modified genomic DNA indicates a high degree of methylation in DU-145 cells and lesser degrees in PC-3 and LNCaP cells, whereas in PrEC the TM promoter is unmethylated. The expression of TM is negatively regulated by NF-κB- and GSK3-β-dependent signalling pathways and positively regulated by retinoic acid and transcription factor Sp1 in PrEC, LNCaP and PC-3 cells, but not in DU-145 cells. However, exposure of DU-145 cells to the demethylating agent, 5-aza-2'deoxycytidine, restores the TM expression and its control by retinoic acid, NF-κB- and GSK3-β-dependent signalling. In conclusion, the study establishes that in prostate cancer cell lines relative to PrEC the TM is down-regulated and that the TM promoter is hypermethylated, which seems to be responsible for the down-regulation and failed regulation of TM expression in DU-145 cells.

PMID:
22406829
DOI:
10.1016/j.canlet.2012.03.001
[Indexed for MEDLINE]

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