Navigation Links
Why Don’t All Moles Progress to Melanoma

Everyone has moles. Most of the time, they are nothing but a cosmetic nuisance. But sometimes pigment-producing cells in moles called melanocytes// start dividing abnormally to form a deadly form of skin cancer called melanoma. About one in 65 Americans born this year will be diagnosed with melanoma at some point during their lifetime.

Scientists know that 30 percent of all melanomas begin in a mole. They know that 90 percent of moles contain cancer-causing mutations. What scientists didn’t know is how melanocytes stop these mutations from triggering the development of cancer.

Maria S. Soengas, Ph.D., and other scientists in the Multidisciplinary Melanoma Clinic at the University of Michigan Comprehensive Cancer Center, have found the answer to this important question in an unexpected place – a structure inside cells called the endoplasmic reticulum, or ER.

“Our results support the direct role of the endoplasmic reticulum as an important gatekeeper of tumor control,” says Soengas, who is an assistant professor of dermatology in the U-M Medical School. “Until now, no one knew there was a connection between ER stress and the very early stages of tumor initiation.”

Results of the U-M study – involving melanocytes from normal human skin and biopsies of non-malignant human moles – are being published in the October issue of Nature Cell Biology.

The endoplasmic reticulum is the cell’s protein production factory. The process begins when chains of amino acids are deposited in the ER membrane in response to coded instructions from genes. Chaperone proteins fold these amino acids into specific shapes. When too many of them build up in the membrane, or when something goes wrong with the folding process, the system gets bogged down. This can stress or even kill the cell.

To prevent this, the ER sends out distress signals to activate what scientists call the unfolded protein response (UPR). This slows the pro tein production process and gets rid of excess incoming amino acids, giving the ER a chance to catch up. If that doesn’t work, the UPR causes the cell to destroy itself in a process called apoptosis.

“Traditionally, the ER’s role was considered to be limited to protein folding or protein modification,” Soengas says. “But scientists like Randal Kaufman, a U-M professor of biological chemistry and co-author on our paper, have found that the ER can sense changes in glucose, nutrients, oxygen levels and other aspects of cellular physiology associated with diseases like diabetes and Alzheimer’s disease.”

“In our study, we found that the ER senses the activity of certain oncogenes in the melanocyte and triggers a response that prevents the malignant transformation of these cells,” Soengas adds.

According to Soengas, the tumor suppressive mechanism induced by the ER in melanocytes with these cancer-causing mutations is premature senescence – a form of “suspended animation” that stops the cell cycle and keeps cells from dividing, but doesn’t kill them.

“The cells are held in check – they don’t die, but they don’t proliferate either,” Soengas explains. “In the case of moles, melanocytes can stay this way for 20 to 40 years or even your whole life. For most of us, just holding cells in an arrested state is sufficient to prevent the development of cancer. That’s why so many people have moles, but few have melanoma.”

In the study, U-M scientists found that the tumor suppressive response in melanocytes varied depending on the type of oncogene being expressed in the cell.

“We found that some oncogenes activated the endoplasmic reticulum, while other oncogenes didn’t,” Soengas says.

In a previous study, Soengas and colleagues found that certain oncogenes use a different senescence mechanism, which doesn’t activate the ER, to block the transformation of melanocytes. Both these mechanisms work in add ition to or independent from other well-known tumor suppressor mechanisms involving apoptosis.

Soengas says the results of the study will be important in helping scientists understand all the different mechanisms melanocytes use to protect themselves against oncogenes. But she cautions that there are no immediate clinical applications for the study and additional research will be required.

In future research, Soengas will attempt to determine exactly how oncogenes trigger the unfolded protein response in malignant and non-malignant skin cells. “By comparing what happens in normal melanoctyes with what happens in melanoma, we may be able to come up with events that are specific for tumor cells, which could be used for future drug development,” she say.


Related medicine news :

1. “Don’t fear long haul flights!” Vascular surgeon tells travelrs
2. Alcohol and Sun Don’t Mi
3. Don’t Blame the High Heels
4. Contraceptive Pills Don’t Result In Weight Gai
5. Love is blind and Seeing is not Believing – Parents Don’t Believe Their Children Are Overweight!!
6. Shriners in London Don’t Intend To Give Up Their Caus
7. Don’t forsake the chicken: Cooked poultry free from bird fl
8. Don’t Chicken Out
9. Safe Cigarettes Developed That Don’t Stain Your Teet
10. Women- Don’t drink and Be Pregnan
11. Caretakers Don’t Use Blood Pressure Drugs Regularl
Post Your Comments:

(Date:6/26/2016)... N.J. (PRWEB) , ... June 27, 2016 , ... Quality ... sources, yet in many ways they remain in the eye of the beholder, according ... (EBO), a publication of The American Journal of Managed Care. For the full issue, ...
(Date:6/26/2016)... ... June 26, 2016 , ... Many women are ... with endometriosis. These women need a treatment plan to not only alleviate symptoms ... can help for preservation of fertility and ultimately achieving a pregnancy. The specialists ...
(Date:6/25/2016)... ... June 25, 2016 , ... First Choice Emergency ... named Dr. Sesan Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm facility. ... Director of our new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical Director ...
(Date:6/24/2016)... ... 2016 , ... A recent article published June 14 on E ... goes on to state that individuals are now more comfortable seeking to undergo not ... as calf and cheek reduction. The Los Angeles area medical group, Beverly Hills Physicians ...
(Date:6/24/2016)... ... ... Global law firm Greenberg Traurig, P.A. announced that 20 Florida attorneys are ... for this recognition are considered among the top 2 percent of lawyers practicing within ... of this year’s Legal Elite Hall of Fame: Miami Shareholders Mark D. Bloom, ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... June 24, 2016 The Academy of Managed ... recommendations that would allow biopharmaceutical companies to more ... that make formulary and coverage decisions, a move that ... new medicines. The recommendations address restrictions in ... on the drug label, a prohibition that hinders decision ...
(Date:6/24/2016)... PUNE, India , June 24, 2016 ... "Pen Needles Market by Type (Standard Pen Needles, Safety ... 12mm), Therapy (Insulin, GLP-1, Growth Hormone), Mode of Purchase ... published by MarketsandMarkets, This report studies the market for ... is expected to reach USD 2.81 Billion by 2021 ...
(Date:6/23/2016)... HOUSTON , June 23, 2016  MedSource ... platform as its e-clinical software solution of choice.  ... the best possible value to their clients by ... nowEDC.  The preferred relationship establishes nowEDC as the ... pricing for MedSource,s full-service clients.  "nowEDC has long ...
Breaking Medicine Technology: