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Lack of 'gatekeeper' protein linked to skin cancer

Date:
May 18, 2011
Source:
North Carolina State University
Summary:
New research shows that a "gatekeeper" protein plays an important role in skin-cancer prevention in humans and lab mice. The protein, C/EBP alpha, is normally abundantly expressed to help protect skin cells from DNA damage when humans are exposed to sunlight. The research shows, however, that the protein is not expressed when certain human skin cancers are present.

New research from North Carolina State University shows that a "gatekeeper" protein plays an important role in skin-cancer prevention in humans and lab mice.

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 skin cancer.

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 function."

In the study, the researchers found that human skin expresses C/EBP alpha as does the pre-cancerous, benign lesion called actinic keratose -- the precursor to skin cancer.

"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 -- and how and why the protein is inactivated in cancerous cells -- marks the next step in his research.

The research was funded by the National Institute of Environmental Health Sciences and the National Cancer Institute. Colleagues from the University of Chicago and Columbia University contributed to the study, as did graduate students and postdocs in Smart's laboratory.


Story Source:

The above story is based on materials provided by North Carolina State University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Elizabeth A. Thompson, Songyun Zhu, Jonathan R. Hall, John S. Hoose, Rakesh Ranjan, Jeanne A. Burr, Robert C. Smart, Yu-Ying He and David M. Owens. C/EBP alpha Expression is Downregulated in Human Nonmelanoma Skin Cancers and Inactivation of C/EBP alpha Confers Susceptibility to UVB-Induced Skin Squamous Cell Carcinomas. Journal of Investigative Dermatology, June 2011

Cite This Page:

North Carolina State University. "Lack of 'gatekeeper' protein linked to skin cancer." ScienceDaily. ScienceDaily, 18 May 2011. <www.sciencedaily.com/releases/2011/05/110518111252.htm>.
North Carolina State University. (2011, May 18). Lack of 'gatekeeper' protein linked to skin cancer. ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2011/05/110518111252.htm
North Carolina State University. "Lack of 'gatekeeper' protein linked to skin cancer." ScienceDaily. www.sciencedaily.com/releases/2011/05/110518111252.htm (accessed April 18, 2014).

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