In the current study, investigators set out to determine whether the increased amount of p53 and enhanced expression of p53 target genes might contribute to the quiescence of cells and their ability to resist chemotherapy. They examined the function of p53 during hematopoiesis and found an important interdependency between p53 and its target gene, MEF, on HSC quiescence.
"Our findings suggest that by targeting those specific genes that control quiescence in cancer cells, we may enhance the anticancer effects of chemotherapy and radiotherapy, thereby promoting their effectiveness," said Dr. Nimer.
In addition, researchers identified two new targets of the p53 protein Necdin and Gfi-1 tumor growth suppressor genes that also regulate quiescence. Researchers lowered the expression of Necdin and Gfi-1 in hematopoietic stem cells lacking MEF and found a significant reduction in the quiescence of those cells. The results suggest that these p53 target genes are functionally responsible for the enhanced quiescence of HSCs in which MEF has been eliminated.
|Contact: Esther Napolitano|
Memorial Sloan-Kettering Cancer Center