Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

High levels of PEA-15 shrink breast cancer tumors

21.04.2009
Mouse model findings indicate protein is new, important target for therapy

Overexpression of PEA-15, which binds and drags an oncoprotein out of the cell nucleus where it fuels cancer growth, steeply reduced breast cancer tumors in a preclinical experiment, researchers at The University of Texas M. D. Anderson Cancer Center reported at the 100th annual meeting of the American Association for Cancer Research.

Human breast cancer grafts in mice dropped to nearly undetectable levels after 35 days when treated with an adenoviral PEA-15 vector that overexpressed the protein in tumors.

"Treated mice had a dramatic response, while tumors continued to grow in control mice," said first author and presenter Chandra Bartholomeusz, M.D., Ph.D., a post-doctoral fellow in M. D. Anderson's Department of Breast Medical Oncology. Bartholomeusz presented the findings at a minisymposium titled "Up and Coming Targeted Biologic Strategies."

"This first animal model experiment demonstrates the therapeutic potential of PEA-15," said senior author Naoto Ueno, M.D., Ph.D., associate professor of breast medical oncology. "PEA-15 is a different way of modulating growth because it's based on location of the protein in the cell rather than, for example, protein regulation by phosphorylation."

Ueno and colleagues previously showed that PEA-15 stymied ovarian cancer in lab experiments, and that high expression of the protein in tumors is tied to improved overall survival. They had also examined PEA-15 expression in 26 breast cancer specimens and found the protein was more heavily expressed in the 13 low-grade tumors analyzed.

In the breast cancer experiments, the team first tested overexpression in three breast cancer cell line cultures. Lines treated with PEA-15 developed 30 to 60 percent fewer colonies of cancer cells than did control cultures. Further analysis of one cell line showed that adenovirally delivered PEA-15 overexpression inhibited cell growth and reduced DNA synthesis.

They also found that activated ERK - a protein active in growth, differentiation and mobility of cells that can fuel cancer growth when in the nucleus - was sequestered in the cell's cytoplasm. This is consistent with previous research by Ueno's team that showed PEA-15 works by binding and dragging ERK and phosphorylated ERK from the nucleus, inducing cell death.

Cell cycle analysis indicated the onset of apoptosis - programmed cell death - in breast cancer cells treated with PEA-15. In the case of ovarian cancer, the team found evidence of death by autophagy - cellular self-consumption - rather than apoptosis. The varied forms of cellular death may indicate that the protein's mechanisms differ from one form of cancer to another, Ueno said.

PEA-15 is a versatile protein, serving multiple cellular functions, including glucose metabolism and regulating the tumor necrosis factor (TNF) pathway in addition to its role regulating ERK, Ueno said.

"We are committed to further developing PEA-15 and making it a druggable target," Ueno said. The team is developing a non-gene therapy treatment because adenovirally delivered gene therapies such as those used to overexpress PEA-15 in the mouse experiments have had less success in humans.

Funding for this research was provided by a Susan G. Komen Postdoctoral Fellowship to Bartholomeusz and a National Cancer Institute grant to Ueno.

Co-authors with Bartholomeusz and Ueno are Linda Yuan, Fumiyuki Yamasaki, M.D., Ph.D., Anna Kazansky, Dongwei Zhang, M.D., PhD, Francisco Esteva, M.D., Ph.D., and Gabriel Hortobagyi, M.D., all of M. D. Anderson's Breast Cancer Translational Research Laboratory and the Department of Breast Medical Oncology; and Savithri Krishnamurthy, M.D., of M. D. Anderson's Department of Pathology.

About M. D. Anderson

The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For four of the past six years, including 2008, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.

Scott Merville | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>