Cancer protein intensifies gene expressions

The protein c-MYC HLH-bZIP distinguishes itself from other cell growth regulators by boosting the expressions of genes already turned on as opposed to switching genes on and off, according to findings in an NIH study.

The c-MYC HLH-bZIP (MYC) protein assists in cell activation, but abnormally high levels of MYC can lead to a variety of cancers, including breast cancer, lung cancer and blood cancers.

Researchers have been unable to explain why abnormal amounts of the cell growth regulator can lead to a wide variety of cancers, according to background information in the study.

Identifying the subtle yet highly sophisticated difference between power switch and universal amplifier offers researchers a new understanding of MYC function and how it influences future treatment efforts in a number of different cancers, the researchers said.

Zuquin Nie, PhD, a research biologist in the Laboratory of Pathology at the NCI, and colleagues investigated MYC function in primary lymphocytes by using specially designed fluorescent proteins that tracked MYC in white blood cells, specifically B cells and T cells.

The researchers chose cells that fight infections because they are affected by abnormal MYC and can transform into lymphoma or myeloma cells, according to the study.

Nie and colleagues exposed the cells to toxins, stimulating an immune response which activated the fluorescent MYC.

Next, they examined the cells at different points to determine which genes the MYC proteins affected.

Researchers found MYC proteins at nearly every expressed gene.

The amount of MYC was influenced by the amount of gene activity prior to immune stimulation, according to Nie and colleagues. Low-activity genes received small boosts from MYC, whereas highly active genes received larger boosts.

“A remarkably simple rule emerged from this quantitative analysis: MYC is not an on-off specifier of gene activity, but is a nonlinear amplifier of expression, acting universally at active genes, except for immediate early genes that are strongly induced before MYC,” the researchers wrote. “This rule of MYC action explains the vast majority of MYC biology observed in literature.”

The investigators validated the relatively simple rule by developing B cells that failed to produce functional MYC. When stimulated, RNA — an indicator of how much protein is being made — failed to increase. However, when researchers stimulated normal B cells, their RNA increased, study results showed.

A treatment strategy for MYC-associated tumors that limits rather than eliminates MYC activity is an approach to consider, the researchers said.

“This discovery offers a unifying idea of how and why abnormal levels of MYC are found in so many different cancer types,” researcher Keji Zhao, PhD, director of the Systems Biology Center at the NHLBI, said in a press release.