Most folks know the hormone erythropoietin (aka EPO) because of its use as a “doping” substance by athletes to illegally gain an edge on their competition through enhanced red blood cell production. Even though we all make at least a little bit of the stuff naturally in lots of our tissues, it seems that athletic committees aren’t the only ones hoping to eradicate EPOs use. New research shows that many cancers would like to see it banned too—they’ll even methylate the EPO promoter to repress its expression.
German researchers deploying real-time PCR found that many tumor cancer cell lines had reduced EPO expression. Bisulfite sequencing and combined bisulfite restriction analysis (COBRA) of the EPO gene revealed that CpG islands in its promoter and enhancer were hypermethylated in most tumor cell lines and tumor tissue samples; and this hypermethylation correlated with reduced EPO expression.
In low oxygen conditions (a trigger for EPO expression), cancers with hypermethylated promoters that were treated with 5-aza-2′-deoxycytidine (Aza)—a DNA methylation inhibitor—started transcribing the EPO gene again. Cancer cells divided more when they ectopically expressed EPO, which makes sense because EPO is involved in many growth-promoting pathways.
The researchers say that although their data only address the epigenetic regulation of EPO in cancers, this could be a way that cancers regulate many other growth-promoting genes.
Find out how EPO may be good for fighting cancer (but bad for sports) at Genes and Cancer, Jan. 2011.