July 30, 2009

Epigenetic Signature Changes In Low Oxygen Levels Could Contribute To Prostate Cancer Development

UCD Conway researchers have characterized epigenetic signature changes in prostate cells under conditions of low oxygen levels that may lead to tumor development. The results of the study published this month in the scientific journal, Human Molecular Genetics may provide important targets for the early detection and manipulation of prostate cancer.

Chronic hypoxia, or low tissue oxygen levels, is a natural feature of the aging prostate either due to declining blood flow to the area or local consumption of oxygen during re-modelling of the organ. It may also be a risk factor in the development of prostate cancer but, to date, the processes involved are not defined.

This study led by Conway Fellow, Dr Amanda McCann, and involving collaborators in UCD Conway Institute as well as teams in St Vincent's University Hospital, the National Centre for Medical Genetics Crumlin and Cancer Research UK Cambridge Research Institute, examined the consequences of chronic hypoxia on prostate cells.

Epigenetic gene regulation refers to changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence.  The group found significant epigenetic and cellular alterations in prostate cells as a result of hypoxia. Cells became more resistant to the natural process of cell death, increasingly able to migrate or invade and also caused the secretion of chemical messengers that are believed to be involved in the growth and survival of prostate tumor cells.  

Epigenetic alterations were also identified across the extent of the genome and involved increased histone acetylation and DNA methylation. These epigenetic processes may promote and maintain the expression of regulatory genes and activation of adaptive pathways that possibly promote tumor development.

Commenting on the significance of the findings, Dr Jenny Watson PhD, a Health Research Board North/South funded postdoctoral scientist and lead author on the publication, said, "Understanding how chronic hypoxia influences global and gene-specific epigenetic programming will provide important insights into the mechanisms of hypoxia-induced cellular changes. The identification of these factors contributing to the initial development of prostate cancer represents important targets for early detection and manipulation in early stage disease".

This research was funded by the Health Research Board in Ireland [HRB NS/2004/2] and the UCD Horizon Scanning Seed funding scheme.


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