Journal article

Oncogenic HRAS suppresses clusterin expression through promoter hypermethylation

P Lund, K Weisshaupt, T Mikeska, D Jammas, X Chen, R-J Kuban, U Ungethum, U Krapfenbauer, H-P Herzel, R Schafer, J Walter, C Sers



Silencing of gene expression by methylation of CpG islands in regulatory elements is frequently observed in cancer. However, an influence of the most common oncogenic signalling pathways onto DNA methylation has not yet been investigated thoroughly. To address this issue, we identified genes suppressed in HRAS-transformed rat fibroblasts but upregulated after treatment with the demethylating agent 5-Aza-2-deoxycytidine and with the MEK1,2 inhibitor U0126. Analysis of gene expression by microarray and Northern blot analysis revealed the MEK/ERK target genes clusterin, matrix metalloproteinase 2 (Mmp2), peptidylpropyl isomerase C-associated protein, syndecan 4, Timp2 and Thbs1 to be repressed ..

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University of Melbourne Researchers