December 8, 2010
Ultraviolet Light Helps Skin Cancer Cells Thrive
The sun's ultraviolet light activates an enzyme that helps skin cancer cells survive and proliferate, researchers report.
The finding shows another way cancer pirates normal body functions as it points toward better treatment for the million new cases of non-melanoma skin cancers diagnosed in the United States annually, said Dr. Wendy Bollag, corresponding author of the study in Oncogene. Bollag is a cell physiologist at the Medical College of Georgia and the Charlie Norwood Veterans Affairs Medical Center."We are living longer and getting a lot of UV radiation in the process," she said of increasing skin cancer rates. Her research shows that UV's ill effects are cumulative and dose dependent: more UV exposure equals more activity by the enzyme protein kinase D. That's another wakeup call about excess sun exposure particularly as we age, Bollag said, and an indicator that protein kinase D inhibitors, already under development for other cancers, may also work for skin cancer.
Skin cells normally make protein kinase D to help regulate growth needed to replace cells that are constantly sloughing off. "The skin has to continually divide to replace cells that get lost to the environment," Bollag said. Even something as benign as wearing clothes prompts skin cell loss and the constant demand for new ones. "So, protein kinase D is good under normal conditions, when it's regulated appropriately. But what can happen is it starts misbehaving," Bollag said.
Its increased activity enables skin cells to survive the constant onslaught of UV radiation, which can be good or bad. "If the damage caused by UV is relatively minor, so the cell can repair it, that's good. You wouldn't want to walk across the street, your skin gets hit by UV, all the cells die and your skin sloughs off," Bollag said.
The downside is that by promoting cell survival, protein kinase D can enable skin cells with a lot of DNA damage to become cancerous by reducing the natural ability of badly damaged skin cells to self-destruct, the researchers show.
Bollag's laboratory previously found that protein kinase D was upregulated in basal cell carcinoma, a common non-melanoma skin cancer. Since sun exposure is the greatest risk factor for basal cell carcinoma, they suspected the link between ultraviolet radiation and protein kinase D.
Now they also have found that pretreating skin cells with antioxidants appears to reduce protein kinase D activation by UV, indicating that reactive oxygen species, or free radicals, also play a role. Free radicals can result from excessive cell activity or oxygen use.
The researchers want to further explore UV's impact on protein kinase D in the more deadly melanoma cancers. They also want to know if, as with hormones, protein kinase D activity normally slows with age. They suspect it does since skin cell turnover slows with age. But it may just be that aging skin cell repair mechanisms maintain skin cell survival but don't repair the sun's damage as well as they once did, Bollag said.
She notes that some UV radiation is good; it's a great source of vitamin D "“ important for bone, breast, vascular health and more "“ which is lacking in many diets. In fact, in some areas of the country, certain types of cancer, such as prostate cancer, are linked to decreased sun exposure.
Non-melanoma skin cancers arise from the keratinocytes, which comprise about 90 percent of skin cells and give skin its primary functions, such as its role as a mechanical barrier. Melanomas occur in the less common melanocytes which give the skin color.
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