New research from North Carolina State Univ. shows that a “gatekeeper”
protein plays an important role in skin-cancer prevention in humans and lab
The protein, C/EBP alpha, is normally abundantly expressed to help protect
skin cells from DNA damage when humans are exposed to sunlight. The NC State
research shows, however, that the protein is not expressed when certain human
skin cancers are present.
Moreover, when the protein is inactivated in special lab mice exposed to
small amounts of the UVB solar radiation, the mice become more susceptible to
Dr. Robert Smart, professor of environmental and molecular toxicology at NC
State and the corresponding author of a paper in the Journal of
Investigative Dermatology describing the research, says that C/EBP alpha
serves as an important “pause button” in cells. If there is any DNA damage,
C/EBP alpha halts the cell-replication process to allow time for cells to
repair themselves to prevent DNA errors from occurring.
“Loss of C/EBP alpha expression is associated with some of the most common
human cancers, including breast and colon cancer,” Smart says. “We think it may
also have a role in tumor suppression in these cancers via its gatekeeper
In the study, the researchers found that human skin expresses C/EBP alpha as
does the pre-cancerous, benign lesion called actinic keratose.
“C/EBP alpha is expressed in normal human skin and in pre-cancerous actinic
keratoses, but something happens when cancerous lesions appear—the protein is
not expressed,” Smart says. “We then asked, ‘Is the loss of C/EBP alpha
contributing to tumor formation?’ The answer seems to be yes.”
Smart and colleagues exposed hairless, genetically modified mice—bred with
C/EBP alpha inactivated—to low doses of the UVB solar radiation. The mice were
highly susceptible to certain common types of skin cancer—squamous cell
carcinomas—with these cancerous tumors developing and growing rapidly.
“If you can figure out how to keep C/EBP alpha turned on, maybe the tumor
would stay in its pre-cancerous state,” Smart says.
Smart adds that figuring out how the protein fulfills its gatekeeper role marks
the next step in his research.