MYC Threshold Found for Tumor Maintenance
At particular level of expression, tumor cells in mice underwent apoptosis and stopped proliferating
THURSDAY, July 3 (HealthDay News) -- In a mouse model of lymphoma, a certain level of MYC expression is necessary to maintain tumorigenesis, and this critical threshold is marked by a shift from cellular proliferation to proliferative arrest and apoptosis, according to research published in the July 1 issue of Cancer Research.
Catherine M. Shachaf, Ph.D., of Stanford University School of Medicine in Stanford, Calif., and colleagues discuss experiments in which they titrated the level of MYC protein expression in mice with lymphoma by controlling the amount of doxycycline in their drinking water. MYC is a transcription factor involved in regulating thousands of genes and is overexpressed in most cancers.
At a certain level of MYC expression, tumor cells stopped proliferation, underwent apoptosis and showed reduced cell size, the investigators found. The researchers identified gene networks associated with cellular proliferation and transformation that were differentially activated below or above this threshold, and they found that proteins with a role in mRNA translation decreased below the threshold level.
"A crucial future direction will be to investigate how different levels of MYC expression influence gene expression and outcome as well as whether this occurs because of different levels of promoter occupancy. Most importantly, we plan to investigate if human tumors also exhibit a threshold level of oncogene expression to maintain tumorigenesis. Our results provide a first glimpse, suggesting that, at least in some cases, partial suppression of the level of MYC overexpression may be sufficient to induce a clinical effect on a tumor," the authors conclude.
A co-author disclosed relationships with Nodality and BD Biosciences, as well as patents related to the technology, and another reported a relationship with Cell Biosciences.