Navigation Links
Vanderbilt researchers find proteins may point way to new prostate cancer drug targets
Date:8/6/2012

Two proteins that act in opposing directions one that promotes cancer and one that suppresses cancer regulate the same set of genes in prostate cancer, Vanderbilt-Ingram Cancer Center researchers have found.

The findings, reported recently in the Journal of Clinical Investigation, point toward potential drug targets and prognostic markers for prostate cancer.

"We are trying to understand the molecular genetics of prostate cancer: what are the genes that are altered in human prostate cancer, and very importantly, how do they lead to cancer when they are changed?" said Sarki Abdulkadir, M.D., Ph.D., associate professor of Pathology, Microbiology and Immunology and of Cancer Biology.

Abdulkadir's lab uses mouse models to probe the molecular pathways involved in prostate cancer.

Two separate projects in the lab unexpectedly came together for this study one led by postdoctoral fellow Philip Anderson, Ph.D., and the other spearheaded by (then) graduate student Sydika McKissic, Ph.D.

Anderson was using genomic approaches to understand how loss of a tumor suppressor protein, called NKX3.1, promotes prostate cancer. NKX3.1 is a transcription factor, meaning that it binds to and regulates the expression of other genes, turning them "on" or "off."

"It is one of the genes most commonly deleted in human prostate cancerand is lost very early," explained Abdulkadir.

Anderson isolated the NKX3.1 protein and identified a set of 9,817 genes that bind to the protein. Of that set, he identified 282 genes that are regulated by the protein i.e., their expression was altered by loss of NKX3.1.

"So we took those genes...and asked 'what is interesting about these genes?'" said Abdulkadir.

Using bioinformatics tools, the investigators found a quarter of the NKX3.1-regulated genes are also bound by a "famous" oncogene called Myc (which, like NKX3.1, is also a transcription factor).

It was previously known that, as human prostate cancer progresses, NKX3.1 levels decrease and Myc levels increase. The research team's findings showed that these two proteins with opposing functions regulated a similar set of genes.

"What we showed in this paper is that actually in many instances, NKX binds and represses these genes while Myc binds and activates them," Abdulkadir said. "The way we think about it is this: Myc is the 'accelerator' and NKX3.1 is the 'brake' (on cancer growth)."

Meanwhile, McKissic was working to develop a mouse model of prostate cancer. However, mice lacking NKX3.1 alone developed early stage prostate cancer, but the disease would not progress. Abdulkadir suspected that another genetic "hit" or mutation was necessary to progress fully to prostate cancer and suspected that Myc was a good candidate for that second "hit" based on how commonly the gene is altered in human prostate cancer.

So McKissic developed a mouse model in which NKX3.1 was deleted and Myc was overexpressed in the specific prostate cells where cancer arises.

She showed that mice with this combination of genetic alterations did progress to advanced cancer and that the same target genes identified in Anderson's project were dysregulated in the mouse model.

To determine clinical relevance, the researchers then analyzed genetic and clinical data from patients with prostate cancer. They found that expression of these target genes was associated with tumor relapse specifically, that suppression of a subset of the target genes may predict relapse.

In addition to potential prognostic indicators of relapse, these "cross-regulated" genes may present therapeutic targets to halt progression of prostate cancer.

Future studies on the roles of the individual target genes could help reveal "which of these genes are bigger players than others for things like therapeutics," Abdulkadir said.


'/>"/>
Contact: Craig Boerner
craig.boerner@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert  

Related medicine news :

1. Vanderbilt study finds obesity linked to kidney injury after heart surgery
2. NIH awards $20 million over 5 years to train next generation of global health researchers
3. Researchers develop a new cell and animal model of inflammatory breast cancer
4. Researchers uncover a viable way for colorectal cancer patients to overcome drug resistance
5. Researchers Find Gene Mutations That May Be a Key to Autism
6. Researchers find evidence of banned antibiotics in poultry products
7. NJ stroke researchers report advances in spatial neglect research at AAN Conference
8. Autism by the numbers: Yale researchers examine impact of new diagnostic criteria
9. Researchers Map Brain Regions Linked to Intelligence
10. Researchers ID Genes That May Determine Mental Illness
11. Researchers Develop Blood Test for Depression
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Vanderbilt researchers find proteins may point way to new prostate cancer drug targets
(Date:6/27/2016)... ... June 27, 2016 , ... ... announced today its affiliation with Tennessee Counseling Association. This new relationship ... of the Tennessee Counseling Association, adding exclusive benefits and promotional offers. , "TCA ...
(Date:6/26/2016)... ... June 27, 2016 , ... Quality metrics are proliferating in ... ways they remain in the eye of the beholder, according to experts who offered ... The American Journal of Managed Care. For the full issue, click here . ...
(Date:6/26/2016)... NC (PRWEB) , ... June 26, 2016 , ... Brent Kasmer, a legally blind and ... to be personalized through a fitness app. The fitness app plans to fix the two ... currently only offer a one size fits all type program , They don’t ...
(Date:6/25/2016)... ... June 25, 2016 , ... The temporary closing of Bruton Memorial Library on June 21 ... brings up a new, often overlooked aspect of head lice: the parasite’s ability to live ... not a common occurrence, but a necessary one in the event that lice have simply ...
(Date:6/25/2016)... ... June 25, 2016 , ... Dr. Calvin Johnson has ... he has implemented orthobiologic procedures as a method for treating his patients. The ... first doctors to perform the treatment. Orthobiologics are substances that orthopaedic surgeons use ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... Calif. , June 24, 2016  Global ... a biopharmaceutical company developing novel therapeutics for the ... needs, today announced the closing of its previously ... common stock, at the public offering price of ... the offering were offered by GBT. GBT estimates ...
(Date:6/24/2016)... , June 24, 2016 ... Markets has announced the addition of the " ... offering. This ... and provides an updated review, including its applications in ... the total market, which includes three main industries: pharmaceutical ...
(Date:6/24/2016)... 2016 The Academy of Managed Care Pharmacy ... that would allow biopharmaceutical companies to more easily share ... formulary and coverage decisions, a move that addresses the ... The recommendations address restrictions in the sharing ... drug label, a prohibition that hinders decision makers from ...
Breaking Medicine Technology: