Lack of 'gatekeeper' protein linked to skin cancer

May 18, 2011 in Cancer

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 from 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 at NC State and the corresponding author of a paper in the 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 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 ," Smart says. "We think it may also have a role in 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.

More information: "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" Elizabeth A. Thompson, et al. Published: June 2011 print edition of Journal of Investigative Dermatology

Abstract
Human epidermis is routinely subjected to DNA damage induced by UVB solar radiation. Cell culture studies have revealed an unexpected role for C/EBP alpha (CCAAT/enhancer-binding protein-alpha) in the DNA damage response network, where C/EBP alpha is induced following UVB DNA damage, regulates the G1 checkpoint, and diminished or ablated expression of C/EBP alpha results in G1 checkpoint failure. In the current study we observed that C/EBP alpha is induced in normal human epidermal keratinocytes and in the epidermis of human subjects exposed to UVB radiation. The analysis of human skin precancerous and cancerous lesions (47 cases) for C/EBP alpha expression was conducted. Actinic keratoses, a precancerous benign skin growth and precursor to squamous cell carcinoma (SCC), expressed levels of C/EBP alpha similar to normal epidermis. Strikingly, all invasive SCCs no longer expressed detectable levels of C/EBP alpha. To determine the significance of C/EBP alpha in UVB-induced skin cancer, SKH-1 mice lacking epidermal C/EBP alpha (CKO alpha) were exposed to UVB. CKO alpha mice were highly susceptible to UVB-induced SCCs and exhibited accelerated tumor progression. CKO alpha mice displayed keratinocyte cell cycle checkpoint failure in vivo in response to UVB that was characterized by abnormal entry of keratinocytes into S phase. Our results demonstrate that C/EBP alpha is silenced in human SCC and loss of C/EBP alpha confers susceptibility to UVB-induced skin SCCs involving defective cell cycle arrest in response to UVB.

Provided by North Carolina State University search and more info website

not rated yet  

Rank not rated yet
Relevant PhysicsForums posts

More news stories

New colonoscope provides ground-breaking view of colon

A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...

Cancer created 46 minutes ago | popularity not rated yet | comments 0

ASCO: combo antibody therapy effective for melanoma

(HealthDay)—Concurrent use of two immune checkpoint antibodies—ipilimumab and nivolumab—may be effective for the treatment of advanced melanoma, according to a proof-of-principal study presented in ...

Cancer created 19 hours ago | popularity not rated yet | comments 0

Risk factors ID'd for poor cutaneous cell CA outcomes

(HealthDay)—The risks of metastasis and death associated with cutaneous squamous cell carcinoma (CSCC) are low, but significant, and risk factors for poor outcome include tumor diameter, invasion beyond ...

Cancer created 20 hours ago | popularity not rated yet | comments 0 | with audio podcast

Physical & emotional impairments common, often untreated in people with cancer

A new review finds cancer survivors suffer a diverse and complex set of impairments, affecting virtually every organ system. Writing in CA: A Cancer Journal for Clinicians, Julie Silver, M.D., associate professor at Harvar ...

Cancer created May 17, 2013 | popularity not rated yet | comments 0

Calif. doc with 'cancer cure' gets 14 years prison (Update)

(AP)—A California doctor has been sentenced to 14 years in federal prison for bilking her patients out of more than $1 million by promising that an herbal supplement could cure late-stage cancer and other diseases.

Cancer created May 17, 2013 | popularity not rated yet | comments 0


New research identifies risks, interventions for children's GI health

An increasing number of U.S. children are experiencing gastrointestinal issues that require interventions to resolve, according to research presented at Digestive Disease Week (DDW).

AIDS science at 30: 'Cure' now part of lexicon

Big names in medicine are set to give an upbeat assessment of the war on AIDS on Tuesday, 30 years after French researchers identified the virus that causes the disease.

For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests

Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...

Melon focus headband turns to Kickstarter for rollout plans

(Medical Xpress)—What if the quality of your work depends more on your focus on the piano keys or canvas or laptop than your musical or painting or computing skills? If target users can be convinced, they ...

Temporal processing in the olfactory system

The neural machinery underlying our olfactory sense continues to be an enigma for neuroscience. A recent review in Neuron seeks to expand traditional ideas about how neurons in the olfactory bulb might encode information about ...

Now we know why old scizophrenia medicine works on antibiotics-resistant bacteria

In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...