On the correlation of CTCF binding and c-myc amplification in human prostate cancer cell lines

2. Abstract BackgroundBackground: One of the hallmarks of prostate cancer development is the amplification of C-MYC copy numbers. It is not yet clear what the driving force behind the activation of C-MYC expression in prostate cancer is. CTCF, which is known for its role as chromatin organiser, is thought to be involved in the activation of C-MYC expression. The affinity of CTCF to its binding site on the DNA is negatively affected by methylation of CpG islands, including its binding site within the promoter sequences of C-MYC. DNA hypermethylation is often found in cancer cells and could therefore be responsible for reduced binding of CTCF at the C-MYC promoter, which can in turn lead to enhanced expression.\n\nResultsHere, the copy number of C-MYC of five different prostate cancer cell lines has been determined by FISH, and the state of methylation of the binding site of CTCF upstream of C-MYC was investigated. The C-MYC locus was shown to be amplified to various degrees in all cell lines, reflecting the copy number of actual tumors very well, but methylation was found to remain unchanged compared to healthy cells in all examined cell lines. Hence, no correlation between C-MYC-copy number and CTCF binding possibilities could be established.\n\nConclusionsThe enhanced expression of C-MYC in prostate cancer cell lines is not affected by CTCF, whose binding presumably still persists. C-MYC activation in prostate cancer must therefore be caused by a disparate mechanism, which also deviates from other well known mechanisms that are seen in Burkitt-Lymphoma, Leukemia and breast cancer.