antiproliferative effects of dna methyltransferase 3b depletion are not associated with dna demethylation抗增殖的影响dna甲基转移酶3 b损耗并不与dna脱甲基作用有关.pdfVIP

Antiproliferative Effects of DNA Methyltransferase 3B Depletion Are Not Associated with DNA Demethylation 1 1,2 2 2 1 2 Sabine Hagemann , Dirk Kuck , Carlo Stresemann , Florian Prinz , Bodo Brueckner , Cora Mund , 2 2 Dominik Mumberg , Anette Sommer * 1 Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany, 2 Global Drug Discovery, Bayer Healthcare Pharmaceuticals, Berlin, Germany Abstract Silencing of genes by hypermethylation contributes to cancer progression and has been shown to occur with increased frequency at specific genomic loci. However, the precise mechanisms underlying the establishment and maintenance of aberrant methylation marks are still elusive. The de novo DNA methyltransferase 3B (DNMT3B) has been suggested to play an important role in the generation of cancer-specific methylation patterns. Previous studies have shown that a reduction of DNMT3B protein levels induces antiproliferative effects in cancer cells that were attributed to the demethylation and reactivation of tumor suppressor genes. However, methylation changes have not been analyzed in detail yet. Using RNA interference we reduced DNMT3B protein levels in colon cancer cell lines. Our results confirm that depletion of DNMT3B specifically reduced the proliferation rate of DNMT3B-overexpressing colon cancer cell lines. However, genome-scale DNA methylation profiling failed to reveal methylation changes at putative DNMT3B target genes, even in the complete absence of DNMT3B. These results show that DNMT3B is dispensable for the maintenance of aberrant DNA methylation patterns in human colon cancer cells and they have important implicati