Navigation Links
Researchers find new culprit in castration-resistant prostate cancer
Date:12/13/2012

BOSTONScientists at Dana-Farber Cancer Institute have discovered a molecular switch that enables advanced prostate cancers to spread without stimulation by male hormones, which normally are needed to spur the cancer's growth. They say the finding could lead to a new treatment for prostate cancers that are no longer controlled by hormone-blocking drugs.

The researchers report in the Dec. 14 issue of Science that the molecular switch occurs in a protein, EZH2, which is increased in these tumors, termed castration-resistant prostate cancers (CRPC).

EZH2 is part of a protein complex that normally shuts off the expression of genes. But in CRPC cells, "It isn't working the way people had thought," said Myles Brown, MD, co-senior author of the report. Instead, EZH2 switches into a different mode, activating cell-growth genes -even in the absence of androgen hormones that spur the dangerous growth and spread of these cancers.

As a result, the researchers suggest that drugs designed to stifle this unexpected function of EZH2 might be effective as a new treatment strategy for CRPC tumors.

Brown's co-senior author is X. Shirley Liu, PhD; together they lead Dana-Farber's Center for Functional Cancer Epigenetics.

Most prostate tumors are fueled by male hormones, or androgens, which interact with a molecule called the androgen receptor in cancer cells. When the receptor receives androgen signals, it transmits orders to the cell's nucleus to divide and grow. Surgical castration or administering drugs that halt androgen production can control cancers that have spread outside the prostate gland.

However, these cancers often escape their need for androgens after a few years of treatment and become resistant. Brown said the tumor cells reprogram the androgen receptors so that they activate cell-growth genes despite the absence of hormone stimulation.

EZH2 is known as an "epigenetic regulator," meaning that it regulates the activity of genes without changing their DNA structure. Previously it was found that EZH2 levels are dramatically increased in late-stage castration resistant prostate cancer, Brown said, but researchers thought the protein was acting primarily to turn off gene activity which is its normal role.

Drugs aimed at blocking EZH2 activity are being tested in other cancers, where they are designed to block the protein's gene-suppressing role. However, they carry a risk of harmful side effects as a result. "But we found that isn't the important function of EZH2 in CRPC," Brown explained. "In these cancers, EZH2 works with the androgen receptor to turn on genes involved with cell growth." As a result, he proposes that inhibitors of EZH2 that avoid targeting its gene-repressor function might be a safe and effective strategy for use in castration-resistant prostate cancers.

Further, said Brown, the EZH2 protein itself is activated by a molecular signaling pathway known as PI3K, or PI3 kinase. Several PI3K inhibitors are in clinical trials at present, and Brown said that a combination of drugs to inhibit both that pathway and the EZH2 protein might be yet another way to attack the resistant prostate cancers.


'/>"/>

Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert  

Related biology news :

1. ASU researchers propose new way to look at the dawn of life
2. New geometries: Researchers create new shapes of artificial microcompartments
3. UGA researchers find algal ancestor is key to how deadly pathogens proliferate
4. Researchers identify new components of the epigenetic code for honey bee development
5. Researchers find new genetic pathway behind neurodevelopmental disorders
6. Researchers investigate impacts of climate change on rare tropical plants
7. Researchers identify proteins that indicate which kidney tumors are most likely to spread
8. Microchoreography: Researchers use synthetic molecule to guide cellular dance
9. Einstein researchers receive 2 Grand Challenges Explorations grants to combat HIV and TB
10. University of Tennessee researchers find fungus has cancer-fighting power
11. UC Davis researchers aid effort to sequence the complex wheat genome
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Researchers find new culprit in castration-resistant prostate cancer
(Date:6/23/2017)... ITHACA, N.Y. , June 23, 2017 /PRNewswire/ ... leader in dairy research, today announced a new collaboration ... reduce the chances that the global milk supply is ... dairy project, Cornell University has become the newest academic ... Supply Chain, a food safety initiative that includes IBM ...
(Date:5/6/2017)... 5, 2017 RAM Group , ... new breakthrough in biometric authentication based on a ... properties to perform biometric authentication. These new sensors are ... created by Ram Group and its partners. This sensor ... supply chains and security. Ram Group is a ...
(Date:4/13/2017)... UBM,s Advanced Design and Manufacturing event in ... and evolving technology through its 3D Printing and Smart ... the expo portion of the event and feature a ... on trending topics within 3D printing and smart manufacturing. ... will take place June 13-15, 2017 at the Jacob K. ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... October 11, 2017 , ... ... granted orphan drug designation to SBT-100, its novel anti-STAT3 (Signal Transducer and Activator ... osteosarcoma. SBT-100 is able to cross the cell membrane and bind intracellular STAT3 ...
(Date:10/10/2017)... ... October 10, 2017 , ... For the second ... a US2020 STEM Mentoring Award. Representatives of the FirstHand program travelled to Washington, ... from US2020. , US2020’s mission is to change the trajectory of STEM education ...
(Date:10/10/2017)... 2017 SomaGenics announced the receipt of a ... RealSeq®-SC (Single Cell), expected to be the first commercially ... microRNAs) from single cells using NGS methods. The NIH,s ... accelerate development of approaches to analyze the heterogeneity of ... techniques for measuring levels of mRNAs in individual cells ...
(Date:10/9/2017)... DIEGO , Oct. 9, 2017  BioTech ... biological mechanism by which its ProCell stem cell ... critical limb ischemia.  The Company, demonstrated that treatment ... amount of limbs saved as compared to standard ... the molecule HGF resulted in reduction of therapeutic ...
Breaking Biology Technology: