Navigation Links
Neuronal regulators offer potential targets for cancer

Boston, Mass. (March 19, 2008) -- Being too brainy can be a bad thing in a junior high cafeteria, where the social hierarchy favors other traits. "Braininess" also causes problems for cells. When a breast cell begins making the proteins normally produced in neurons, for example, it can acquire cancerous properties.

Now, researchers in Stephen Elledge's laboratory at Harvard Medical School (HMS) have identified some of the switches that control this transformation, providing promising new therapeutic targets in some types of cancer. Their results appear in the March 20 issue of Nature.

"These switches play an important physiologic role in neural development and pathologic role in cancer," says first author Thomas Westbrook, who is now an assistant professor at Baylor College of Medicine. "I'm optimistic that we can use small molecules to control them."

In a previous study, Westbrook showed that a protein called REST--which keeps neural programs silent in most parts of the body--serves as a tumor suppressor.

"He's now identified a protein that promotes tumor growth by tagging REST for destruction, thereby activating neural programs," says Elledge, who holds primary appointments in the HMS Department of Genetics and at Brigham and Women's Hospital.

If the protein REST worked at a club, he would be a bouncer, preventing dozens of rowdy patrons from causing trouble. REST serves as a "master repressor," keeping numerous neural genes silent in breast cells, lung cells, etc, where they could wreak havoc. When REST disappears, these genes roar to life, pushing cells to become more like neuron precursor cells.

But cells outside the nervous system keep neural genes silent for a reason. When neural genes get switched on in breast cells anchored to surfaces, for example, they acquire the ability to live without the anchoring that is essential for normal cells to survive. That is, they can grow in suspension, which is a classical characteristic of cancer cells.

After uncovering this role, Westbrook used a technique called RNA interference (RNAi) to search for proteins that reduce REST levels. He reasoned that these proteins might promote tumor formation if expressed outside the nervous system.

The RNAi screen netted a known tumor promoter called ß-TRCP. Further genetic tests revealed that ß-TRCP binds directly to REST, tagging it for destruction. But REST must be primed with a particular molecule called phosphate for this interaction to occur.

"If we can prevent ß-TRCP from binding to REST, we may be able to treat certain tumors that display neuronal gene expression profiles," says Elledge, who is also a member of the HMS-Partners HealthCare Center for Genetics and Genomics and investigator with the Howard Hughes Medical Institute. "Such profiles are remarkably common in epithelial cancers, such as breast cancer and ovarian cancer."

"This discovery is particularly exciting because the scientific community knows how to target enzymes that add and remove phosphate groups from proteins with small molecules," says Westbrook. "Big pharmaceutical companies have devoted lots of resources to accomplishing this task."

Information about the interaction between ß-TRCP and REST might also aid researchers in the embryonic stem cell field.

"It's hard to control the differentiation of embryonic stem cells into specialized cells such as neurons," says Westbrook. "If one could prevent ß-TRCP from tagging REST for destruction, one could potentially keep embryonic stem cells from turning into neurons. Alternatively, one might be able to make neurons more efficiently by quickening REST destruction."


Contact: Alyssa Kneller
Harvard Medical School

Related medicine news :

1. Abbott Researchers Target Neuronal Nicotinic Receptors for Treatment of Pain and Cognition
2. Low level of neuronal receptor linked to mild cognitive impairment and Alzheimers disease
3. Deficient regulators in the immune system responsible for type 1 diabetes
4. Promising new TB drug given special status by US and European regulators
5. AARP Calls on State Regulators to Reject Proposed Settlement of TXU Buyout
6. Waters Offers U.S. Water Authorities Complimentary Drinking Water Testing for the Presence of Pharmaceuticals
7. Mirion Technologies to Showcase New Product Offerings for the Nuclear Industry During 10th Annual China International Nuclear Industry Exhibition
8. SearchMedica Offers Medical Professionals Six New Specialized Clinical Web Searches
9. Cardinal Health, GE Healthcare Broaden Relationship to Offer Greater Access to Myoview(TM) Imaging Agent
10. Peapod Offers First Ever Virtual Nutritionist
11. Agilysys Hosts IBM Specialist at Health Care Webinar Offering Data Storage Solutions
Post Your Comments:
(Date:11/25/2015)... ... November 25, 2015 , ... "When I underwent ... bras were incredibly uncomfortable," said an inventor from Bronx, N.Y. "In order to ... the patent-pending RECOVERY BRA for added comfort and support. The bra is easier ...
(Date:11/25/2015)... ... November 25, 2015 , ... Bcureful—a non-profit organization devoted to ... raising public awareness of the disorder while helping to bring expert medical care ... to bolster progress at the Tuberous Sclerosis Complex Center at Ann & Robert ...
(Date:11/24/2015)... Florida (PRWEB) , ... November 25, 2015 , ... ... planning and monitoring. Their Care Plan software creates an agreement between the ... patient care plan, including financial, scheduling, monitoring, notification, and projections. Click ...
(Date:11/24/2015)... ... November 24, 2015 , ... Young patients with a ... Dr. Angela Wolfman and Dr. Kedar S. Lele, who are pediatric dentists in ... and fillings, the WaterLase iPlus 2.0™ system causes minimal discomfort and bleeding to the ...
(Date:11/24/2015)... ... November 25, 2015 , ... ... solutions for drugs, biologics, consumer health and global clinical supply services, today announced ... upcoming Clinical Trial Supply East Asia Conference, to be held at the InterContinental ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... Nov. 24, 2015  Thanks to a donor with ... Mary,s Medical Center,s Sister Diane Grassilli Center for Women,s ... in San Francisco . ... stepped forward with a gift of $617,320 that allowed ... Mammography with Tomosynthesis and Whole Breast Ultrasound. Tomosynthesis, three-dimensional ...
(Date:11/24/2015)... 24, 2015  Array BioPharma Inc. (Nasdaq: ... Officer, Ron Squarer , will present at ... York.  The public is welcome to participate in ... BioPharma website.Event:Piper Jaffray Annual Healthcare ConferencePresenter:  , Ron ... 2015Time:1:30 p.m. Eastern Time Webcast: , ...
(Date:11/24/2015)... and VANCOUVER, Nov. 24, 2015 /PRNewswire/ - ESSA ... EPIX ) announced today that the first patient ... of EPI-506 as a treatment for metastatic castration-resistant prostate ... and Canada.  --> the ... In the Phase 1/2 clinical trial, ESSA intends ...
Breaking Medicine Technology: