Navigation Links
Targeting aggressive prostate cancer
Date:8/14/2013

(SACRAMENTO, Calif.) A team of researchers from UC Davis, UC San Diego and other institutions has identified a key mechanism behind aggressive prostate cancer. Published on August 14, 2013 in Nature, the study shows that two long non-coding RNAs (PRNCR1 and PCGEM1) activate androgen receptors, circumventing androgen-deprivation therapy. In their active state, these receptors turn on genes that spur growth and metastasis, making these cancers highly treatment-resistant. The study illustrates how prostate cancer can thrive, even when deprived of hormones, and provides tempting targets for new therapies.

"Androgen-deprivation therapy will often put cancer in remission, but tumors come back, even without testosterone," said contributor Christopher Evans, professor and chair of the Department of Urology at the UC Davis School of Medicine. "We found that these long non-coding RNAs were activating the androgen receptor. When we knocked them out, cancer growth decreased in both cell lines and tumors in animals."

Evans' UC Davis group was part of a larger team, led by Michael Geoff Rosenfeld, professor at the Howard Hughes Medical Institute in the School of Medicine at UC San Diego, which has been eager to determine how androgen-dependent cancers become androgen-independent (also called castration-resistant). These prostate cancers are very aggressive and usually fatal, but their continued growth, despite being deprived of hormones, is just now being better understood. It's not unlike removing the key from a car ignition, only to have the vehicle re-start on its own.

In this case, the aberrant starting mechanisms are long non-coding RNAs, a class of genetic material that regulates gene expression but does not code for proteins. Using patient samples from UC Davis, the group determined that both PRNCR1 and PCGEM1 are highly expressed in aggressive tumors. These RNAs bind to androgen receptors and activate them in the absence of testosterone, turning on as many as 617 genes.

Further investigation determined that one of these long non-coding RNAs is turning on androgen receptors by an alternate switching mechanism, like a car with a second ignition. This is critically important because many prostate cancer treatments work by blocking a part of the androgen receptor called the C-terminus. However, PCGEM1 activates another part of the receptor, called the N-terminus, which also turns on genes with bad results.

"The androgen receptor is unique, if you knock out the C-terminus, that remaining part still has the ability to transcribe genes," said Evans.

In addition, about 25 percent of these cancers have a mutated version of the androgen receptor that has no C-terminus. These receptors are locked in the "on" position, activating genes associated with tumor aggression.

Regardless of the receptor's status, PRNCR1 and PCGEM1 are crucial to prostate cancer growth. In turn, knocking out these RNAs has a profound impact on gene expression, both in cell lines and animal models. The team used complementary genetic material, called antisense, to knock out the RNAs and observe how the tumors and cells responded. In each case, there was a direct relationship between RNA activity, gene expression and cancer growth.

"These long non-coding RNAs are a required component for these castration-resistant cancers to keep growing," said Evans. "Now we have preclinical proof of principle that if we knock them out, we decrease cancer growth."

The research team's next step is developing treatments that specifically target these long non-coding RNAs. That process has already begun.

"Most treatments for castration-resistant prostate cancer will get us around two to three years of survival," said Evans. "We rarely cure these patients. The tumor will continue to evolve resistance mechanisms. But now that we have additional insight into what's activating these receptors, we can begin developing new types of therapies to prevent it."


'/>"/>

Contact: Dorsey Griffith
dorsey.griffith@ucdmc.ucdavis.edu
916-734-9118
University of California - Davis Health System
Source:Eurekalert

Related medicine news :

1. Nanodrug targeting breast cancer cells from the inside adds weapon: Immune system attack
2. Cancer research brief: Targeting pancreatic cancer drug resistance
3. Targeting errant immune system enzyme kills myelodysplastic cells
4. hCGTreatments / Diet Doc hCG Diets & Weight Loss Plans Offer Improved hCG Diet Plans Capable of Targeting Stubborn Belly Fat Now Linked With Decreased Bone Density
5. hCGTreatments / Diet Doc hCG Diets & Weight Loss Plans Now Offer New Weight Loss Diets that Educate Patients, Targeting Weight Gained During Childhood and Adolescence
6. Overcoming resistance to anti-cancer drugs by targeting cell powerhouses
7. Study Shows Dual Targeting of HER2 and HR-positive Metastatic Breast Cancer Improves Survival Rates
8. Drugs targeting blood vessels may be candidates for treating Alzheimers
9. Changing shape makes chemotherapy drugs better at targeting cancer cells
10. Cleveland Clinic study shows bariatric surgery restores pancreatic function by targeting belly fat
11. Daimer Ships Steam Pressure Washer For Pest Control Industry Targeting Food Service Kitchens
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/31/2016)... ... ... A book about the self-discovery of one’s limitless creative power, “ Unleash Your ... give readers the courage they need to embrace their creativity and unleash it as ... my life to learn and create what I set my heart with no limits ...
(Date:5/31/2016)... (PRWEB) , ... May 31, 2016 , ... "ProDrop 3D ... projects to the next level," said Christina Austin - CEO of Pixel Film Studios. ... Studios. With ProDrop 3D Abstract have the ability to generate and manipulate three-dimensional shapes ...
(Date:5/31/2016)... ... ... According to recent statistics, there are nearly half a million physical therapists ... physical therapy professional and every clinic has a duty to perform at the highest ... competitive industry is also essential. The solution that many physical therapy leaders turn to ...
(Date:5/31/2016)... (PRWEB) , ... June 01, 2016 , ... ... “ Psoriasis and smoking: links and risks ”. , As corresponding author Professor ... on the relation between smoking habits and psoriasis. Smoking influences the onset and ...
(Date:5/31/2016)... ... May 31, 2016 , ... ... that considers individuals’ genetic characteristics and the physical and behavioral worlds in ... in sync. In personalized medicine, diagnosing an individual’s disease depends on accurately ...
Breaking Medicine News(10 mins):
(Date:5/31/2016)... May 31, 2016 Aloe vera ... food, cosmetics and pharmaceuticals, with global volume to surpass ... 1.6 Bn. Demand for aloe vera extracts ... yogurts will continue its upward momentum in 2016 as ... boost positive sentiment on aloe vera, with wide-ranging applications ...
(Date:5/31/2016)... , May 31, 2016 The global ... coupled with surging prevalence of deaths from chronic diseases. According ... By Region, By Country): Opportunities and Forecasts (2016-2021) - (By ... Orthopaedic, Cardiovascular, Plastic Surgery, Wound Care); By Region-North America, ... UK, Germany , Italy ...
(Date:5/31/2016)... May 31, 2016 , Isansys  Lifecare, ... its Patient Status Engine wireless patient monitoring platform, as it ... Germany , Scotland and ... 2 nd generation system, launched earlier this year, is now ... , , This new technology significantly enhances ...
Breaking Medicine Technology: