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.

Source-Newswise
SRM
'"/>




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:
*Name:
*Comment:
*Email:


(Date:2/10/2016)... St. Louis, Missouri (PRWEB) , ... February 10, ... ... 11-14, 2016, in San Diego, will bring together more than 200 of the ... in healthcare for the future. , “The true benefit of the Forum is ...
(Date:2/10/2016)... ... 10, 2016 , ... AHRA: The Association for Medical Imaging ... Fox will serve as keynote speaker at the organization’s 2016 Spring Conference. Fox’s ... more effectively communicate with their own organizational staff and leadership. , “I ...
(Date:2/10/2016)... ... February 10, 2016 , ... Everseat has joined the award-winning ... to physicians. The integration will enable Allscripts users to post open appointments to ... mobile app. , The partnership gives Everseat substantial added power to help Allscripts ...
(Date:2/10/2016)... ... February 10, 2016 , ... The recreational use of marijuana has been ... still face a lot of restrictions as to where they can smoke pot. ... use” and that cannabis “may not be consumed openly or publicly.” , Given the ...
(Date:2/10/2016)... ... February 09, 2016 , ... According to a recent article published ... number of patients under the age of 30. According to Southern California based medical ... and may indicate an overall shift in the rapidly growing social acceptance of cosmetic ...
Breaking Medicine News(10 mins):
(Date:2/10/2016)... The campaign aims to ensure 2,50,532 ... reach the milestone of their 5 th birthday   --> ... between the ages of 2 - 5 years reach the ... campaign aims to ensure 2,50,532 children ... of their 5 th birthday   India , ...
(Date:2/9/2016)...  Misonix, Inc. (NASDAQ: MSON ), an ... markets innovative therapeutic ultrasonic products for spine surgery, ... surgery and other surgical applications, today announced financial ... half of fiscal year 2016 ended December 31, ... --> Highlights for the second quarter and ...
(Date:2/9/2016)... YORK, Pa., Feb. 9, 2016  Unilife Corporation ("Unilife" or "Company") ... of injectable drug delivery systems, today announced its financial results for ... 2015). ... Revenue for the ... million in the same period last year.  Cash receipts from customers ...
Breaking Medicine Technology: