All in the Nucleus: Stopping the Transformation of Chromatin in Cancer Cells
The human cell's nuclear DNA is compacted 10,000-fold by the ordered assembly of proteins, such as histones, which form a structure called chromatin. The chromatin controls how, when, and where the cell's genetic information is used.
How chromatin is modified in cancer cells is of particular interest to Canada Research Chair Dr. James Davie. He studies the mechanisms by which a cell transmits signals from its surface to the interior of its nucleus producing remodelling of the chromatin and alterations in gene expression.
Scientists already know that certain signal transduction pathways are implicated in a significant percentage of human cancers and that these pathways are stimulated by oncoproteins that are involved in changing normal cells into cancer cells. Dr. Davie himself discovered that certain oncoproteins activate a signal transduction pathway in cancer cells that result in the activation of chromatin-modifying enzymes in the nucleus, leading to changes in the chromatin and expression of specific genes.
Now, Dr. Davie is exploring the mechanisms regulating the location of these chromatin-modifying enzymes in the cell and the processes involved in regulating their activity and targeting specific genes. It has been found that by inhibiting the activity of those chromatin-modifying enzymes, called histone deacetylases, one can change the expression of a select set of genes that are important in the ability of cancer cells to multiply. Therefore, Dr. Davie is developing new strategies to arrest the activity of these enzymes and prevent the growth of cancer cells.
Davie's research group is part of the Manitoba Breast Cancer Research Centre, which houses the Manitoba Breast Cancer Tumour Bank. Through studying proteins isolated from cell nuclei taken from cancerous and non-cancerous cells, these scientists believe that the identification of biomarkers in the early detection of breast cancer is an attainable goal.