Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Study Proposes New Ovarian Cancer Targets

Published: Friday, March 14, 2014
Last Updated: Friday, March 14, 2014
Bookmark and Share
Researchers from Brown University propose that TAFs may be important suspects in the progression of ovarian cancer.

In the complex genomic and molecular conspiracy that gives rise to ovarian cancer, what if researchers have been missing a whole set of suspects because they’ve been hiding in plain sight? That’s the argument made by Brown University biologists in a new paper that combines evidence from original research and prior studies to raise new suspicions about a set of proteins that assist in regulating gene expression.

Scientists need such new leads in their investigation of ovarian cancer, the most deadly reproductive cancer. Mortality has remained tragically steady since the last major therapeutic breakthrough came in the 1990s. Pursuing the evidence that these proteins may be involved could allow researchers to make new progress.

“There is just not a lot of headway being made in ovarian cancer,” said pathobiology graduate student Jennifer Ribeiro, lead author of the study online in Frontiers in Oncology. “This is a different perspective. It’s a high-risk but potentially high-reward scenario.”

Ribeiro’s proteins of interest are called TAFs. Traditionally biologists have seen them merely as cogs in a universal and generic system that enables enzymes to transcribe genes into RNA, said study senior author Richard Freiman, associate professor of medical science at Brown. But in the new paper he and Ribeiro propose that TAFs may not merely be going about their droning business as ovarian tumors go haywire. They may be meaningfully associated with the calamity.

Guilt by many associations?
An early hint of a link between TAFs and ovarian cancer emerged in a 2011 Nature paper, coauthored by Brown University computer science researchers. Ribeiro followed up on that tip to make some of her main original findings in the new paper. By poring over the cBioPortal database of cancer genomics, she found that several TAFs are often significantly overexpressed or underexpressed in ovarian cancer. TAF2 amplifications, copy number gains, and expression increases are present in 73 percent of tumors. TAF4 is amplified or upregulated in 66 percent of tumors, and TAF4B is amplified or upregulated in 26 percent. TAF9, meanwhile, is rendered significantly less expressed in 98 percent of ovarian tumors.

The ups and downs of TAF expression alone might not be that interesting if TAF activity didn’t have any mechanistic influence in cancer cell biology. But in her review of scores of studies and further original research, Ribeiro presents reasons to believe that in specific tissues and contexts around the body, these TAFs take on roles that are relevant.

“They are not just general transcription factors,” Freiman said. “They do much more specific things.”

The worst tumors are ones in which cells have “dedifferentiated,” which means they’ve lost their specific identities and reverted to a more generic, stem cell-like form. Sure enough, Ribeiro and Freiman have found that TAFs such as TAF4 and TAF4B are downregulated when stem cells differentiate. That makes their upregulation in ovarian tumors suspicious.

TAF4B also emerges as a cancer suspect in the study because of its apparent role in promoting cell proliferation, a major problem in the runaway cell multiplication in tumors. Lindsay Lovasco, a postdoctoral fellow at Brown and second author of the study, ran an experiment in mouse models where she removed some of the liver and measured whether TAFs expression changed while the tissue regenerated. Expression of Taf4b (the gene in mice) did increase significantly. Also, in human ovarian granulosa cell-derived tumors, in collaboration with Dr. Barbara Vanderhyden at the University of Ottawa, Ribeiro found that TAF4B expression correlates strongly with Cyclin D2 expression, a protein that specifically promotes granulosa cell proliferation.

Even more suspicion falls on TAF4B based on Ribeiro’s finding published last year in Biology of Reproduction that estrogen upregulates the protein in mouse ovaries and in estrogen-supplemented mouse ovarian tumors. In humans, long-term estrogen hormone replacement therapy has been associated with a greater risk of ovarian cancer.

Cell growth and death
Meanwhile, TAF2 may have its own cancer-related modus operandi. Work by other researchers has shown that TAF2 boosts the expression of a protein called C-SRC, that promotes cell growth and proliferation. Perhaps not surprisingly, other studies have found that C-SRC is overexpressed in ovarian tumors.

“Given these results, it is possible that TAF2 overexpression could increase transcription of C-SRC in some ovarian tumors,” the researchers wrote.

But what of TAF9, which unlike its brethren seems to become notably less expressed in ovarian cancers? There, too, there is a suspicious mechanistic connection to ovarian cancer. TAF9 is a co-activator of the protein p53, which promotes cell death, a handy thing to promote in tumors. But p53 activity is also suppressed in ovarian cancer. Together, these changes may help ensure the survival of ovarian cancer cells.

Ribeiro and Freiman readily acknowledge that the case they build is circumstantial, but they argue it is more than enough for cancer researchers to look at TAFs as potential targets in their search for new treatments.

“We’ve compiled this hypothesis and provided the data that we think is relevant, but there still is much that is not known about it,” Ribeiro said.

In the lab now, Ribeiro and Freiman are testing the effects in human ovarian cancer cells of manipulating TAF expression and function.

The American Cancer Society (grant DMC-117629) and the National Institutes of Health (grant RO1HD065445) and the Canadian Institutes of Health Research Grant (grant MOP-111194 supported the research.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More Than 4,600+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Growing Stem Cells More Safely
Nurturing stem cells atop a bed of mouse cells works well, but is a non-starter for transplants to patients – Brown University scientists are developing a synthetic bed instead.
Tuesday, May 03, 2016
Developing Nanoscale Biosensors
A technique called plasmonic interferometry has the potential to enable compact, ultra-sensitive biosensors for a variety of applications.
Wednesday, February 17, 2016
Mathematical Model Helps Show How Zebrafish Get Their Stripes
The iconic yellow and blue stripes of zebrafish form dynamically as young fish develop and grow. A mathematical model developed by Brown University researchers helps to show how pigment cells interact to form the pattern.
Tuesday, December 01, 2015
Tissue Engineers Recruit Cells to Make Their Own Strong Matrix
Extracellular matrix is the material that gives tissues their strength and stretch. It’s been hard to make well in the lab, but a Brown University team reports new success. The key was creating a culture environment that guided cells to make ECM themselves.
Tuesday, November 10, 2015
Proteins with ALS, Cancer Role Do Not Assume a Regular Shape
Our cells contain proteins, essential to functions like protein creation and DNA repair but also involved in forms of ALS and cancer, that never take a characteristic shape, a new study shows.
Monday, October 12, 2015
Study Backs Flu Vaccinations for Elderly
Brown University researchers found vaccines well matched to the year’s flu strain significantly reduce deaths and hospitalizations compared to when the match is poor, suggesting that vaccination indeed makes a difference.
Wednesday, August 26, 2015
Web App Helps Researchers Explore Cancer Genetics
Brown University computer scientists have developed a new interactive tool to help researchers and clinicians explore the genetic underpinnings of cancer.
Monday, July 27, 2015
Tapeworm Drug Shows Promise Against MRSA
A new study shows that a drug already approved to fight tapeworms in people, effectively treated MRSA superbugs in lab cultures and in infected nematode worms.
Monday, April 27, 2015
A New Wrinkle For Cell Culture
Researchers at Brown University have developed an advanced technique for cell culturing that uses sheets of wrinkled graphene to mimic the complex 3-D environment inside the body.
Friday, April 24, 2015
Gold By Special Delivery Intensifies Cancer-Killing Radiation
Researchers at Brown and URI have demonstrated what could be a more precise method for targeting cancer cells for radiation.
Wednesday, April 15, 2015
DNA ‘Cage’ Could Improve Nanopore Technology
Scientists at Brown University have designed a nanoscale cage that can trap a single DNA strand and allow before-and-after sequencing of the same DNA strand in research trials.
Wednesday, February 11, 2015
New Technology Makes Tissues, Someday Maybe Organs
A new device for building large tissues from living components of three-dimensional microtissues borrows on ideas from electronics manufacturing.
Wednesday, January 07, 2015
New Research Unlocks a Mystery of Albinism
A team led by Brown University biologists has discovered the way in which a specific genetic mutation appears to lead to the lack of melanin production underlying a form of albinism.
Thursday, December 18, 2014
If CD8 T Cells Take on One Virus, They’ll Fight Others Too
The findings suggest that innate immunity changes with the body’s experience and that the T cells are more versatile than thought.
Saturday, October 25, 2014
A ‘Clear’ Choice for Clearing 3-D Cell Cultures
A new study is the first to evaluate three chemical technologies for making animal tissues see-through side-by-side for use with engineered 3-D tissue cultures.
Thursday, September 04, 2014
Scientific News
Platelets are the Pathfinders for Leukocyte Extravasation During Inflammation
Findings from the study could help in the prevention and treatment of inflammatory pathologies.
ASMS 2016: Targeting Mass Spectrometry Tools for the Masses
The expanding application range of MS in life sciences, food, energy, and health sciences research was highlighted at this year's ASMS meeting in San Antonio, Texas.
Benchtop Automation Trends
Gain a better understanding of current interest in and future deployment of benchtop automated systems.
Manufactured Stem Cells to Advance Clinical Research
Clinical-grade cell line will enable development of new therapies and accelerate early-stage clinical research.
Dengue Virus Exposure May Amplify Zika Infection
Researchers at Imperial College London have found that the previous exposure to the dengue virus may increase the potency of Zika infection.
Gender Determination in Forensic Investigations
This study investigated the effectiveness of lip print analysis as a tool in gender determination.
Identifying Novel Types of Forensic Markers in Degraded DNA
Scientists have tried to verify the nucleosome protection hypothesis by discovering STRs within nucleosome core regions, using whole genome sequencing.
Proteins in Blood of Heart Disease Patients May Predict Adverse Events
Nine-protein test shown superior to conventional assessments of risk.
Higher Frequency of Huntington's Disease Mutations Discovered
University of Aberdeen study shows that the gene change that causes Huntington's disease is much more common than previously thought.
Starving Stem Cells May Enable Scientists To Build Better Blood Vessels
Researchers from the University of Illinois at Chicago College of Medicine have uncovered how changes in metabolism of human embryonic stem cells help coax them to mature into specific cell types — and may improve their function in engineered organs or tissues.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,600+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!