Does 5hmC Help Cancer Get Stemmy?
There’s quite a bit of speculation on the significance of 5-hydroxymethylcytosine (5hmC) in regulating gene expression, yet the actual function of 5hmC has yet to be determined. A study mapping the distribution of this epigenetic modification may shed some light on its role in differentiation and carcinogenesis, and will certainly supply fodder for further research and discussion.
Srinivasan Yegnasubramanian and his team at Johns Hopkins found that across a range of embryonic and adult tissue, cells that were more stem- and progenitor-like had greatly reduced staining for the 5hmC modification when compared with more differentiated cells.
Similarly, tumor cells—which have presumably become de-differentiated—evinced significantly less 5hmC than their normal counterparts.
Their other key findings:
- In hierarchically arranged tissue like the colon, cervix, oral mucosa, and bladder, more differentiated luminal/apical cells showed greater evidence of 5hmC modification than did the more regenerative basal cells.
- Similarly, the CD34– bone marrow–derived hematopoietic cell compartment, where more mature blood cells are found, exhibited much higher 5hmC content than did the CD34+ compartment representing stem and progenitor cells. These findings may indicate a role of 5hmC in differentiation.
- There was a profound reduction in 5hmC staining in breast, colon, and prostate cancer cells when compared to adjacent normal cells in the same samples. This was not associated with either grade or stage, suggesting that global loss of 5hmC may be an early event in carcinogenesis.
For more findings and the immunohistochemical staining technique that made it all possible, see Oncotarget, August 2011.
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