Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Biomarker in an aggressive breast cancer is identified

20.08.2014

Overactive protein in basal-like carcinoma offers target for new therapeutics

Two Northwestern University scientists have identified a biomarker strongly associated with basal-like breast cancer, a highly aggressive carcinoma that is resistant to many types of chemotherapy. The biomarker, a protein called STAT3, provides a smart target for new therapeutics designed to treat this often deadly cancer.

Using breast cancer patient data taken from The Cancer Genome Atlas, molecular biologists Curt M. Horvath and Robert W. Tell used powerful computational and bioinformatics techniques to detect patterns of gene expression in two cancer subtypes. They found that a small number of genes are activated by STAT3 protein signaling in basal-like breast cancers but not in luminal breast cancers.

Basal-like cancer is a category that includes a number of different breast cancers, including the highly aggressive form called triple negative cancer.

"You can't treat breast cancer as one disease," Horvath said. "Cancer describes many molecular processes that have gone wrong. We have teased out from large amounts of data that STAT3 activity correlates with distinct patterns of gene expression in one type of breast cancer but not in another."

The findings are published today (Aug. 19) in the online early edition of the journal Proceedings of the National Academy of Sciences (PNAS).

The results suggest a clinical study should be conducted of a STAT3-inhibiting drug in patients with basal-like and luminal cancers, Horvath said. Currently there are no pills or injections targeting STAT3 for breast cancer patients.

Horvath is a professor of molecular biosciences in Northwestern's Weinberg College of Arts and Sciences and a professor of microbiology-immunology and of medicine at Northwestern University Feinberg School of Medicine.

Previous research has found the STAT3 protein to be overactive in many breast cancers, but its role has not been well understood. Horvath and Tell's research is the first reported study to compare breast cancer subtypes and gene expression patterns associated with STAT3 in the tumors of human patients.

Horvath emphasized that this is a statistical analysis and the findings need to be verified with careful laboratory and clinical experiments. He plans to conduct such a study with colleagues at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

"The Cancer Genome Atlas is a really rich and growing database of publicly available data created to help us understand cancer," said Horvath, who is a program co-leader of the Signal Transduction in Cancer program at the Lurie Cancer Center. "It allows basic scientists to ask interesting questions about cancer and contribute to clinical care."

Horvath and Tell observed that there are many clearly visible patterns of common gene expression -- where certain genes are turned on and certain genes are turned off -- in the basal-like cancers. Those clear patterns were not seen in the luminal cancers.

"This opens up the possibility that cancer subtype-specific signaling is driven by STAT3 and that STAT3 inhibitors may be more effective in patients diagnosed with basal-like cancers than in those with luminal cancers," Horvath said.

STAT3 stands for "signal transducer and activator of transcription 3," a transcription factor (a protein) encoded by the STAT3 gene in humans. In addition to its known roles in cancerous cells, STAT3 also is an essential mediator of cytokine and growth factor signals in normal cells that are important for diverse processes including immunity and inflammation.

Tell, a postdoctoral fellow in Horvath's lab, had a strong interest in cancer and was very skilled at computational bioinformatics. To design the study, he combined these two elements with the long-time focus of Horvath's lab on STAT3, which has been implicated in cancer in general, as both a causative agent and a survival factor.

Horvath and Tell identified 84 genes that are expressed differently in basal-like cancer tumors as compared to luminal cancer tumors. These genes are highly representative of the immune response and inflammation processes, Horvath said, and consistent with the role of STAT3.

Tell and Horvath's intensive analysis used data from 825 breast cancer patients from across the country, each with hundreds of data points. The data included protein expression, protein phosphorylation, which indicates which signaling pathways are activated, and messenger RNA and microRNA expression.

To sort through the vast amounts of data, the researchers took advantage of Quest, a high-performance computing system at Northwestern. The computer cluster they used offered the equivalent of the processors and random-access memory (RAM) of eight powerful desktop computers linked together.

The title of the paper is "Bioinformatic analysis reveals a pattern of STAT3-associated gene expression specific to basal-like breast cancers in human tumors." Horvath and Tell are the authors of the paper.

Megan Fellman | Eurek Alert!
Further information:
http://www.northwestern.edu

Further reports about: Biomarker Cancer aggressive breast factor findings genes processes tumors

More articles from Life Sciences:

nachricht During HIV infection, antibody can block B cells from fighting pathogens
14.08.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht First study on physical properties of giant cancer cells may inform new treatments
14.08.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

'Building up' stretchable electronics to be as multipurpose as your smartphone

14.08.2018 | Information Technology

During HIV infection, antibody can block B cells from fighting pathogens

14.08.2018 | Life Sciences

First study on physical properties of giant cancer cells may inform new treatments

14.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>