Navigation Links
Thomas Jefferson University researchers discover new pathways that drive metastatic prostate cancer
Date:12/21/2012

PHILADELPHIAElevated levels of Cyclin D1b could function as a novel biomarker of lethal metastatic disease in prostate cancer patients, according to a pre-clinical study published ahead of print on December 21 in the Journal of Clinical Investigation by researchers at the Kimmel Cancer Center at Jefferson.

The group, headed by Karen E. Knudsen, Ph.D., Professor and Hilary Koprowski Chair, Departments of Cancer Biology, Urology, and Radiation Oncology at Thomas Jefferson University and Deputy Director for Basic Science at the KCC, found that Cyclin D1b, a variant of the cell cycle regulator Cyclin D1a, functions independently of the cell cycle to promote metastasis in both early and late stage prostate cancer.

Rather, Cyclin D1b, but not Cyclin D1a, regulates a large gene network, the researchers found, which was shown to cooperate with androgen receptor (AR) signaling to fuel metastatic progression in multiple models of prostate cancer.

Studies have shown that Cyclin D1b expression is elevated in early stages of prostate cancer (in up to 30% of primary disease), and researchers have now demonstrated that this occurs more frequently in late stage castration-resistant prostate cancer: up to 80%.

Cyclin D1b expression is also highly correlated with that of the pro-metastatic gene SNAI2 (Slug), which the group identified as regulated by cooperative signaling between Cyclin D1b and AR.

"Numerous clinical and pre-clinical studies have effectively demonstrated that AR signaling is critical for progression to metastatic disease, but our knowledge of AR targets which can induce metastatic phenotypes is limited," said Dr. Knudsen. "Our data describe how cross talk between the cell cycle and AR can rewire the AR signaling axis to enhance the expression of genes which elicit metastasis in both early and castration resistant prostate cancer models."

"We found that Cyclin D1b can directly promote AR dependent expression of the gene SNAI2 (Slug), which dramatically increased metastatic events to soft tissues in animal models," she added.

Metastatic castration resistant prostate cancer represents the most lethal form of the disease, which arises when AR is reactivated despite continued hormone therapy.

Soft tissue metastasis to the liver and lung represents a particularly aggressive form of prostate cancer, whose presence predicts for decreased survival time in prostate cancer patients.

Currently, there is little knowledge as to how these metastatic events occur, and identification of pathways and biomarkers of this lethal event could greatly benefit prostate cancer patients.

Using various in vitro and in vivo models, researchers found that Slug enhances the ability of cells to colonize soft tissues, which resulted in a higher incidence of metastasis in the liver and lung.

Given the inability to manage AR signaling in metastatic castration resistant prostate cancer, Slug driven pathways could be leveraged to dramatically limit the incidence of soft tissue metastasis and improve patient morbidity and mortality, researchers believe.

"Identification of AR driven pathways which mediate metastatic progression represents a significant leap forward in our attempts to effectively manage prostate cancer progression," said Dr. Knudsen. "Cyclin D1b and Slug can likely be used as biomarkers to identify patients with an increased risk of metastasis, and will eventually provide us with novel "druggable" targets downstream of AR and Slug which can be exploited to dramatically reduce the incidence of these lethal metastatic tumors."


'/>"/>

Contact: Steve Graff
stephen.graff@jefferson.edu
215-955-5291
Thomas Jefferson University
Source:Eurekalert  

Related biology news :

1. The IPCC Report on Climate Change - Swedish professor Thomas Sterner selected as 1 of the experts
2. Game changing diagnostic & prognostic prostate cancer genetic tests revealed by Jefferson
3. Carin Görings remains identified by researchers at Uppsala University
4. University of Alberta research working towards treatment for aortic aneurysms in the abdomen
5. University of Tennessee study predicts extreme climate in Eastern US
6. University of Illinois receives grant to study ozone resistance in corn
7. Mercyhurst University study probes impact of climate change on ectotherms
8. University of Illinois to improve crop yield through photosynthesis in a new global effort
9. University of Chicagos Graeme Bell receives international diabetes prize
10. University of Tennessee researchers find fungus has cancer-fighting power
11. University of Tennessee engineering professor looks to whirligig beetle for bio-inspired robots
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Thomas Jefferson University researchers discover new pathways that drive metastatic prostate cancer
(Date:6/14/2017)... , June 15, 2017  IBM (NYSE: IBM ) ... international tech event dedicated to developing collaboration between startups and ... on June 15-17. During the event, nine startups will showcase ... value in various industries. France ... the international market, with a 30 percent increase in the ...
(Date:5/6/2017)... 2017 RAM Group , Singaporean ... breakthrough in biometric authentication based on a ... to perform biometric authentication. These new sensors are based ... by Ram Group and its partners. This sensor will ... chains and security. Ram Group is a next ...
(Date:4/17/2017)... NXT-ID, Inc. (NASDAQ: NXTD ) ("NXT-ID" ... its 2016 Annual Report on Form 10-K on Thursday April 13, ... ... the Investor Relations section of the Company,s website at http://www.nxt-id.com ... http://www.sec.gov . 2016 Year Highlights: ...
Breaking Biology News(10 mins):
(Date:9/22/2017)... ... September 22, 2017 , ... ... host a booth at premier packaging event PACK EXPO International in Las Vegas ... Machinery Manufacturers Institute (PMMI). , At this year’s PACK EXPO at the Last ...
(Date:9/21/2017)... ... 21, 2017 , ... Dr. Greg Leyer, Chief Scientific Officer of UAS Labs, ... presentation is at 12:10pm in the Probiotics Resource Center, Mandalay Bay Expo Hall. ... discuss how probiotics have shown impressive data in areas outside the gut including heart ...
(Date:9/21/2017)... ... September 21, 2017 , ... When a downtown Greenville portion ... swift and efficient thanks to the continuing efforts of members of the Reedy ... than 50 stakeholders, including officials from area counties and cities, Renewable Water Resources ...
(Date:9/20/2017)... ... 20, 2017 , ... Diversity focused business accelerator, The Refinery , announced ... to uncover the top technology-driven, women-led startups in Boston, MA, New Haven/Hamden, CT, and ... entrepreneurial events going on that week – in Boston, it will be part of ...
Breaking Biology Technology: