Harvard / Dana-Farber Cancer Institute Study: Tanning Protects Against Skin Cancer

[Ezliving_Jim]

'Guardian of the genome' protein found to underlie skin tanning

May also influence human fondness for sunshine

BOSTON—A protein known as the "master watchman of the genome" for its ability to guard against cancer-causing DNA damage has been found to provide an entirely different level of cancer protection: By prompting the skin to tan in response to ultraviolet light from the sun, it deters the development of melanoma skin cancer, the fastest-increasing form of cancer in the world.

In a study in the March 9 issue of the journal Cell, researchers at Dana-Farber Cancer Institute report that the protein, p53, is not only linked to skin tanning, but also may play a role in people's seemingly universal desire to be in the sun – an activity that, by promoting tanning, can reduce one's risk of melanoma.

"The number one risk factor for melanoma is an inability to tan; people who tan easily or have dark pigmentation are far less likely to develop the disease," says the study's senior author, David E. Fisher, MD, PhD, director of the Melanoma Program at Dana-Farber and a professor in pediatrics at Children's Hospital Boston. "This study suggests that p53, one of the best-known tumor-suppressor proteins in our body, has a powerful role in protecting us against sun damage in the skin."

In a study published last year, Fisher and his colleagues found that ultraviolet (UV) radiation from the sun causes skin cells called keratinocytes to make and secrete a hormone called alpha-MSH, which attaches to nearby skin cells called melanocytes and spurs them to produce skin-darkening pigment called melanin. The chain of events within keratinocytes that leads to alpha-MSH production, however, was a mystery.

Investigators knew that alpha-MSH is created when another protein, known as pro-opiomelanocortin (or POMC), is split apart. They also knew that the amount of POMC within cells rises sharply when they're exposed to UV rays. But they didn't know what caused the POMC to increase.

One possibility was p53. When Fisher and his colleagues examined the section of the gene for POMC that promotes production of the protein, they found it meshed nicely with p53 – suggesting that when p53 docks there, it revs up POMC production. Additional evidence came when the researchers exposed human and mouse keratinocytes to UV radiation: After six hours, levels of both POMC and p53 were far higher than normal, and the level of pigment-stimulating alpha-MSH was 30 times above normal.

Further experiments clinched the case for p53's role in tanning. When researchers inserted p53 into keratinocytes, POMC levels rose dramatically. When they delivered UV radiation to mice whose keratinocytes lacked p53, POMC production was not induced and the mice did not tan.

The implications of the research go beyond tanning. A common skin condition, especially among the elderly, is the development of small, dark spots that are unrelated to sun exposure. The spots arise when groups of cells begin producing pigment in response to repeated stress or irritation of the skin. Although not dangerous, the condition can be a cosmetic problem, depending on its location.

"Our research offers a potential explanation of how this condition – known as post-inflammatory hyperpigmentation, or age spots – occurs," Fisher says. "We know that it occurs as a result of stress, and p53 is a classic 'stress' protein, going into action when cells experience stress-related DNA damage. What we've learned about p53 suggests that it may trigger the hyperpigmentation process."

There is even the possibility that p53 protects against skin damage in a second – and previously unsuspected – way. The protein not only causes skin to tan in response to sunlight, it may also underlie people's desire to spend time in the sun.

The same process that causes POMC to produce alpha-MSH also leads to the production of b-endorphin, a protein that binds to the body's opiate receptors and may be associated with feelings of pleasure. "Even as p53 is causing skin to tan during sunlight exposure, it may also affect neuronal circuits," Fisher says. "These proteins may provide an explicit link between the regulation of tanning and of mood. It raises the question of whether p53-mediated induction of beta-endorphin is involved in sun-seeking behavior, which often increases skin cancer risk."

###

The study's lead author is Rutao Cui, MD, PhD, of Dana-Farber and Children's Hospital. Co-authors include Hans Widlund, PhD, Erez Feige, PhD, Jennifer Lin, MD, Dara Wilensky, Vivien Igras, and John D'Orazio, MD, PhD, formerly of Dana-Farber and Children's and now at the University of Kentucky College of Medicine; Scott Granter, MD, of Dana-Farber and Brigham and Women's Hospital; Claire Fung, MD, of Massachusetts General Hospital; and Carl Schanbacher, MD, of Brigham and Women's.

The research was supported by a grant from the National Institutes of Health, and the Doris Duke Charitable Foundation.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

Source: http://www.eurekalert.org/pub_releas...i-ot030507.php

[Ezliving_Jim]

Video from Dana-Farber Cancer Institute http://www.dana-farber.org/video-pla...discussing+p53

http://www.dana-farber.org/abo/news/...n-tanning.html

[Ezliving_Jim]

This story hit the street!

http://news.google.com/news?hl=en&nc....php&scoring=d

[Ezliving_Jim]

The Study: Full Text: http://www.cell.com/content/article/...92867407001857

PDF: http://download.cell.com/pdfs/0092-8...7407001857.pdf

[Ezliving_Jim]

"Tanning Addiction" Explained.

There is even the possibility that p53 protects against skin damage in a second — and previously unsuspected — way. The protein not only causes skin to tan in response to sunlight, it may also underlie people's desire to spend time in the sun.
The same process that causes POMC to produce α-MSH also leads to the production of β-endorphin, a protein that binds to the body's opiate receptors and may be associated with feelings of pleasure. "Even as p53 is causing skin to tan during sunlight exposure, it may also affect neuronal circuits," Fisher says. "These proteins may provide an explicit link between the regulation of tanning and of mood.

[Ezliving_Jim]

This is huge stuff.

From this day forward, it is a whole new world we are living in.

We have come to the end of the tunnel into the light of the Sun. And it is good.

[Ezliving_Jim]

[Ezliving_Jim]

Everybody, please DIGG this story: http://digg.com/health/Study_Tanning..._Skin_Cance r

[solman]

Great news for an industry that's been taking a beating in the press for such a long time. There will probably be a number of nay-sayers, but let's hope this is just the beginning of the positive news. Now, let's all jump in our best UV bed and get tanned!

[Ezliving_Jim]

Dermaterrorist Beauty Queen, Brittany Lietz, Miss Maryland is holding a press conference in MD today.

[Din]

"This might explain addictive behaviors associated with sun-seeking or the use of tanning salons," Fisher said.
Understanding the suntan process could lead to products that allow safe tanning without exposure to damaging UV radiation, even in people who don't otherwise tan, the researchers said.
The findings could also provide a way to identify drugs that restore the response of p53 when it is defective.

Why would they ruin a good review on tanning........He himself says that tanning helps prevent it and then he says that because tanning is damaging...they will try and a safe way of tanning without exposing ourselves to damanging UV radiation......like make a drug to duplicate the effects of a tan in your skin. That way you don't have to go tanning basically....how can you tan without exposing yourself to UV? Is there something else that can duplicate UV that is not UV? And i don't mean just the colour.....because this insn't about the colour for them.....it's about the process that takes place when you are exposed to UV.


What...are we gonna be bubble boys.

[Ezliving_Jim]

Originally Posted by Ezliving_Jim

Everybody, please DIGG this story: http://digg.com/health/Study_Tanning..._Skin_Cance r

Thanks for nothing.

[Ezliving_Jim]

Suntan Gene May Explain Sun Worship

Sun-Loving Gene Spurs Skin to Tan and Might Make People Crave Sunshine

By Miranda Hitti
WebMD Medical News
Reviewed by Louise Chang, MD



March 8, 2007 -- An anticancer gene that moonlights as a suntan gene may partly explain why people crave sunlight and even become addicted to tanning.

Scientists report that the p53 gene, which works to curb tumors, also triggers the chemical chain reaction that makes the skin tan when exposed to ultraviolet (UV) light.

The p53 gene spurs the tanning process to reduce UV damage, note the researchers, who included David Fisher, MD, PhD, of Boston's Dana-Farber Cancer Institute and Harvard Medical School.

Fisher's team found that mice without the p53 gene weren't able to tan when exposed to UV light.

And when the p53 gene triggers the tanning process, it also boosts the release of beta-endorphin, one of the body's "feel-good" chemicals.

"The induction of beta-endorphin appears to be hard-wired to the tanning pathway," Fisher says in a Cell Press news release. "This might explain addictive behaviors associated with sun-seeking or the use of tanning salons."

The study appears in Cell, along with an editorial by experts including Moshe Oren, PhD, of the molecular cell biology department at the Weizmann Institute in Rehovot, Israel.

One day, skin lotions may be able to activate p53 just enough to trigger tanning without allowing UV damage, the editorialists note.

In the Cell Press news release, Fisher says he is involved in a small biotechnology company working to develop such a product.

SOURCES: Cui, R. Cell, March 9, 2007; vol 128: pp 853-864. Oren, M. Cell, March 9, 2007; vol 128: pp 826-828. News release, Cell Press. News release, Dana-Farber Cancer Institute.

[Ezliving_Jim]

SCIENCE NEWS
March 09, 2007

A Protein Twofer That Triggers Tanning and Protects against Skin Cancer

Researchers find that a protein activated to repair DNA damage also activates tanning, which can protect against melanoma

By Nikhil Swaminathan

Image: © ISTOCKPHOTO/SANG NGUYEN

PROTECTIVE LAYER: Scientists have determined that while it fixes damage to DNA caused by UV rays, the protein p53 also controls the mechanism for tanning. A powerful protein known as p53 has long been considered the master regulator of the genome because of its amazing ability to repair damaged DNA. Now scientists at Harvard's Dana-Farber Cancer Institute have discovered that p53 not only mends genetic material but also kicks off the chemical cascade that results in tanning.

The researchers report in Cell that when p53 is activated (in response to DNA damage caused by the sun's ultraviolet (UV) rays and other factors), it triggers production of alpha-MSH, a hormone that then prompts production of melanin, or pigment. Recognizing that p53 is the linchpin of this chain of events could result in a way to "give people tans without needing the sun" (or creams or sprays to artificially color their skin), says senior study author David Fisher, director of Dana-Farber's Cutaneous Oncology and Melanoma Program.

In many types of cancer, p53 is disabled and cannot fulfill its role as a tumor suppressor. Deprived of their ability to fix new DNA damage, defective cells often become tumor cells and proliferate unchecked. In the case of skin cancer—which Fisher notes is "the most common and most preventable" form of the disease—the ability to tan is an extremely strong predictor of cancer susceptibility: Fair-skinned people who are more likely to burn than tan in the sun are at higher risk of developing skin cancer than individuals who tan easily.

In work published last year, the Dana-Farber group found that alpha-MSH, needed to induce melanin production, does not come from melanocytes (melanin-producing cells in the skin). They believe the hormone, instead, is produced in keratinocytes, the most common type of skin cells. The reason: they found broken alpha-MSH receptors on the surface of melanocytes in subjects with an inability to tan.

Other lab work had shown that p53 activates during tanning. And, sure enough, when the Dana-Farber team probed the protein pro-opiomelanocortin (POMC)—which splits to make several hormones including alpha-MSH—it discovered "a perfect p53 binding element there," Fisher says. When testing both mouse and human keratinocytes in vitro, the team observed that after six hours of exposure to UV radiation, p53, POMC and alpha-MSH levels had all jumped dramatically, with the latter's rising 30 times higher than normal. The finding was confirmed in knockout mice missing the gene that codes for p53: Without the protein, POMC was never activated, the mice did not tan (on their hairless ears and tails), and eventually they all developed melanomas.

"What we were stumbling into here was actually a role for p53 in absolutely normal cells," Fisher says, "and it's a normal physiologic response that happens anytime any of us walks out of the house in the morning." He adds that people have a "love-hate relationship" with UV rays, which stimulate vitamin D production needed to keep bones strong and healthy, but also cause potentially deadly skin cancer and premature wrinkling.

Barbara Gilchrest, chair of the Department of Dermatology at Boston University School of Medicine, says that the new findings demonstrate that the p53 system is a broad-response mechanism that has both reparative and preventative properties for DNA damage.

"When you damage DNA in cells, they not only work very hard to fix that DNA, but they also work hard to prepare the cell and tissue to be resistant to future DNA damage," she says. "Once you have that tan, your DNA is better protected for the next time that you're out in the sun, because of that melanin cover over the nucleus shielding it from UV rays that would damage [the] DNA inside."

Fisher says that, in theory, the p53 pathway could be a "druggable" one. "In fact, one of the directions that we're taking to use this information is to try to identify small molecules that could potentially be delivered topically," he reveals, "to either increase or decrease pigmentation through interfering [with] or mimicking this pathway."

Source

[Editor-in-Chief]

The Sunny Side of p53


Moshe Oren 1,* and Jiri Bartek 2,*

1 Department of Molecular Cell Biology, Weizmann Institute, Rehovot, Israel
2 Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Copenhagen, Denmark
*Correspondence: moshe.oren@weizmann.ac.il (M.O.), jb@cancer.dk (J.B.)
DOI 10.1016/j.cell.2007.02.027

http://www.cancer.dk/NR/rdonlyres/E6...ren_Bartek.pdf