Skin Cancer Cells Appear To Thrive On Ultraviolet Light

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Main Category: Melanoma / Skin Cancer
Also Included In: Cancer / Oncology;  Dermatology
Article Date: 08 Dec 2010 - 2:00 PDT


Non-melanoma skin cancer cells appear to thrive on ultraviolet light because it boosts an essential DNA repair enzyme that helps them stay alive and multiply, according to a new study from the US that revealed yet another way that cancer cells exploit natural cell functions.

The study was the work of researchers from the Medical College of Georgia and the Charlie Norwood VA Medical Center, both in Augusta, Georgia, and appeared on 6 December as an advance online publication in the journal Oncogene.

Corresponding author Dr Wendy Bollag, a cell physiologist at both research centers, and colleagues investigated the enzyme protein kinase D (PKD), which plays an important role in skin biology by regulating the growth of new cells and repairing DNA in damaged cells.

Non-melanoma skin cancers form in keratinocytes, which comprise about 90 per cent of skin cells. Melanomas form in the less common melanocytes, the cells responsible for skin color.

In previous studies, Bollag and colleagues had already established that PKD was upregulated in BCC or basal cell carcinoma, a common non-melanoma skin cancer. And since the biggest risk factor for BCC is exposure to the sun, they wondered if there was a link between PKD and sunlight.

In this study they found that the sun's ultraviolet B or UVB rays appear to increase PKD activity in a dose-dependent manner, that is more exposure equals more activity. But while this process is essential for skin repair and renewal as we constantly shed cells to the environment, when it goes awry, it can give cancer a chance to grow.

As Bollag explained to the press:

"The skin has to continually divide to replace cells that get lost to the environment."

Even wearing clothes causes the skin to lose cells and creates demand for new ones, said Bollag.

"So, protein kinase D is good under normal conditions, when it's regulated appropriately. But what can happen is it starts misbehaving," she added.

By "misbehaving" Bollag means they found that under certain conditions, PKD even repaired skin cells with a lot of DNA damage, preventing them from self-destructing and being cleared away by the immune system, and thus increasing the chance they will become cancerous.

Using cell cultures, they verified that PKD activity was induced by UVB light, and they also found that pretreatment with antioxidants appeared to reduce the activity, suggesting that free radicals or reactive oxygen species, by-products of excess cell activity or oxygen use, also play a part.

"We are living longer and getting a lot of UV radiation in the process," said Bollag, explaining that she and her colleagues also found that the effects were cumulative and dose-dependent, that is more UV exposure was linked to more PKD activity.

She said this was another "wake up call" urging us to be careful with sun exposure as we age, and that drugs that inhibit the activity of PKD, already under development for other cancers, may also work for skin cancer.

Bollag and colleagues also established that the path through which UVB increased PKD activity was that which involves "Src family tyrosine kinases" rather than "protein kinase C (PKC)".

They concluded that:

"... our data indicate that UVB irradiation of keratinocytes induces Src-mediated activation of PKD, which protects cells from UVB-stimulated apoptosis, providing a possible explanation for the observed upregulation of PKD in BCC."

Bollag and colleagues now want to research the effect of UV on PKD in the more deadly melanoma cancers, and to find out if PKD activity slows with age, as other hormones do. They have a hunch that it does, because cell turnover slows with age.

But what they are interested in is finding out whether as we age, the mechanisms that repair skin cells focus more on survival and and less on sun damage.

Bollag stressed that it was important to get some exposure to UV light. It's a good source of vitamin D, which we can't get from our food and is essential for bone, breast and blood vessel health, among others.

In fact, Bollag pointed out, in some parts of the US, some types of cancer such as prostate cancer, have been linked to lower sun exposure.

"Ultraviolet B irradiation and activation of protein kinase D in primary mouse epidermal keratinocytes."
S N Arun, I Kaddour-Djebbar, B A Shapiro, W B Bollag.
Oncogene, advance online publication 6 December 2010.
DOI:10.1038/onc.2010.540

Additional source: Medical College of Georgia.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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