With this information, we can begin to understand why the methylation of So 1 could serve as a master regulator of CSC invasion, thereby controlling its potential to undergo EMT and further metastasize. Additional analysis using the GEO database deter mined that both So 1 and Stat3 are e pressed at higher levels in metastatic prostate cancer tissues and not Bm . Overall, we demonstrate that SO 1 is an epigenetically regulated target involved in the pro gression of prostate cancer, and is involved in signaling via the STAT3 pathway. Discussion The process of epigenetic regulation by DNA methyla tion involves covalent modification of cytosine nucleo tides at the C5 position in specific areas of CpG dinucleotides. The majority of methylated CpG dinucleo tides are present in heterochromatic regions, and thus are une pressed in the genome.
The process of methylation in mammals evolved as a method of silen cing genes when their e pression is not required. For e ample, the process of genomic imprinting involves DNA methylation where one allele of a gene, either maternal or paternal, is silenced. This process only affects a few hundred genes within the genome, most Carfilzomib of which encode for genes that regulate embryonic and neo natal growth. Likewise, a number of CpG islands on one chromosome are methylated during a process called chromosome inactivation. This process ensures an equal amount of gene e pression between males and females. Using this model of invasion, we currently have devel oped a method to analyze differences in global CpG promoter methylation between total prostate cancer cells and their invasive population using promoter tiling arrays from Agilent.
We identified a small subset of genes which were found to be differentially methylated between non invasive and invasive LNCaP and DU145 cell lines. The results were highly intriguing because the majority of the genes normally function during human development. Based on previous data, these invasive cells demonstrated charac teristics of true cancer stem cells. It is becoming more evident that CSCs are not governed by the same type of genetic regulation as normal stem cells, and arguably may be an epithelial cell that has up regulated pathways that have been previously observed in true stem cells. To determine the epigenetic profile of these invasive prostate cancer cells and putative TICs, we determined which genes are differentially methylated. The appearance of So 1 as one epigenetically regu lated target presented the most interesting finding of this investigation.