A team of researchers have reported sun's ultraviolet radiation plays a key role in proliferation and survival of skin cancer cells. Ultraviolet radiation activates an enzyme protein kinase D which is up-regulated in carcinoma.
Research by Dr. Wendy Bollag, corresponding author of the study 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 report has been published in Oncogene.