Featured Research

from universities, journals, and other organizations

Loss of tumor suppressor SPOP releases cancer potential of SRC-3

Date:
April 1, 2013
Source:
Baylor College of Medicine
Summary:
Mutations in a protein called SPOP disarm it, allowing another protein called steroid receptor coactivator-3 to encourage the proliferation and spread of prostate cancer cells, researchers report.

Mutations in a protein called SPOP (speckle-type POZ protein) disarm it, allowing another protein called steroid receptor coactivator-3 (SRC-3) to encourage the proliferation and spread of prostate cancer cells, said researchers led by those at Baylor College of Medicine in a report that appears online in Proceedings of the National Academy of Sciences.

Normally SPOP acts as a tumor suppressor gene by marking SRC-3 for destruction, said Dr. Nicholas Mitsiades, assistant professor of medicine -- hematology/oncology and molecular and cellular biology, and corresponding author of the report. SRC-3 is an oncogene or cancer-promoting gene that fosters the growth of cancer cells and their spread or metastasis.

"The protein SPOP is normally there to decrease the levels of SRC-3," said Mitsiades, who is also a member of the Dan L. Duncan Cancer Center at BCM. About a year ago, several groups reported that mutations in SPOP were the most common single point mutation or change in a single nucleotide or base pair (A,T,C,G) that is part of the "alphabet" of DNA or the genetic material of prostate cancer tumors.

What Mitsiades and his group found was that mutated SPOP is no longer an effective suppressor of the cancerous effects of SRC-3. He and his colleagues found the mutation in both the primary or original prostate cancer and in the metastatic tumors that it spawned.

In laboratory studies they showed that when cells produce high levels of normal SPOP, SRC-3 is potently degraded and no longer available to encourage prostate cancer growth.

Mitsiades said that it remains to be examined whether the SPOP mutations affect the prognosis for patients with prostate cancer and their response to treatment.

"To make things more difficult, there is not just one SPOP mutation," he said. "There are many different mutations. Our study and some other data as yet unpublished shows that while all mutations act similarly as far as the mechanism of action, all are not equally potent in their effect. That means additional research needs to be done to examine whether different mutations carry a different prognoses," he said.

"An important question for us is how can you treat prostate cancer with an SPOP mutation," he said.

The mutation results in a loss of function because the mutated gene cannot carry out its task of reducing SRC-3 levels.

"Right now we are not good at replacing something with drugs," he said. "We are much better at inhibiting functions. If we could inhibit SRC-3, then we might overcome the cancer-promoting effects of the mutations in SPOP."

Dr. Bert O'Malley, chair of molecular and cellular biology at BCM and a co-author of the report, is working on inhibitors of SRC-3.

Those inhibitors are important because SRC-3 plays a role in many cancers, including breast cancers, said Mitsiades. It could prove an important target for treatment of many cancers -- along with breast and prostate tumors.

"Its regulation is quite complex," he said. "It can be degraded and SPOP is only one mechanism by which that occurs."

Others who took part in this work include Chuandong Geng, Bin He, Sue Anne Chew, Martin Zimmermann, Richard Bond, John Shou, Chao Li, David Lonard and, Cristian Coarfa, all of BMC; Limei Xu, Christopher E. Barbieri, Mirjam Blattner, Mark A. Rubin, Pengbo Zhou and Francesca Demichelis, all of Weill Cornell Medical College of Cornell University in New York; and Vijay Kumar Eedunuri of Adrienne Helis Malvin Medical Research Foundation in New Orleans, La. Demichelis is also with Centre for Integrative Biology, University of Trento, Italy.

Funding for this work came from the Prostate Cancer Foundation; the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD 8818); the Conquer Cancer Foundation of the American Society of Clinical Oncology Young Investigator and Career Development Awards and a Pilot/Feasibility Program of the Diabetes & Endocrinology Research Center (P30-DK079638) at Baylor College of Medicine. Mitsiades is a Dan L. Duncan Scholar, a Caroline Wiess Law Scholar and a member of the Dan L. Duncan Cancer Center (supported by the NCI Cancer Center Support Grant P30CA125123) and the Center for Drug Discovery at Baylor College of Medicine. The Adrienne Helis Malvin Medical Research Foundation also contributed through its direct engagement in the continuous active conduct of medical research in conjunction with Baylor College of Medicine.


Story Source:

The above story is based on materials provided by Baylor College of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Baylor College of Medicine. "Loss of tumor suppressor SPOP releases cancer potential of SRC-3." ScienceDaily. ScienceDaily, 1 April 2013. <www.sciencedaily.com/releases/2013/04/130401151033.htm>.
Baylor College of Medicine. (2013, April 1). Loss of tumor suppressor SPOP releases cancer potential of SRC-3. ScienceDaily. Retrieved April 16, 2014 from www.sciencedaily.com/releases/2013/04/130401151033.htm
Baylor College of Medicine. "Loss of tumor suppressor SPOP releases cancer potential of SRC-3." ScienceDaily. www.sciencedaily.com/releases/2013/04/130401151033.htm (accessed April 16, 2014).

Share This



More Health & Medicine News

Wednesday, April 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com
Cognitive Function: Is It All Downhill From Age 24?

Cognitive Function: Is It All Downhill From Age 24?

Newsy (Apr. 15, 2014) A new study out of Canada says cognitive motor performance begins deteriorating around age 24. Video provided by Newsy
Powered by NewsLook.com
How Mt. Everest Helped Scientists Research Diabetes

How Mt. Everest Helped Scientists Research Diabetes

Newsy (Apr. 15, 2014) British researchers were able to use Mount Everest's low altitudes to study insulin resistance. They hope to find ways to treat diabetes. Video provided by Newsy
Powered by NewsLook.com
Carpenter's Injury Leads To Hundreds Of 3-D-Printed Hands

Carpenter's Injury Leads To Hundreds Of 3-D-Printed Hands

Newsy (Apr. 14, 2014) Richard van As lost all fingers on his right hand in a woodworking accident. Now, he's used the incident to create a prosthetic to help hundreds. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins