Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify 4 new targets for breast cancer

12.06.2009
New mouse models will help deploy experimental drugs against LPA receptors, autotaxin

Four suspects often found at the scene of the crime in cancer are guilty of the initiation and progression of breast cancer in mice that are resistant to the disease, a team led by scientists at The University of Texas M. D. Anderson Cancer Center reports in the June edition of Cancer Cell.

"We have a smoking gun" that shows it's no coincidence the three protein receptors and the enzyme that makes them are abnormally expressed in many types of cancer, said Gordon Mills, M.D., Ph.D., professor and chair of M. D. Anderson's Department of Systems Biology and senior author of the paper.

"We've compiled lots of evidence that they are associated with cancer, what's been missing is proof that they could cause cancer," Mills said. "There are no questions left, they should be targeted."

The four are three lysophosphatidic acid (LPA) receptors (LPA1, LPA2, and LPA3) and the LPA-producing enzyme, autotaxin. "Lysophosphatidic acid", Mills said, "is the single most potent known cellular survival factor." LPA binds to a series of G protein-coupled receptors to spark normal cell proliferation, viability, production of growth factors and survival. The Cancer Cell paper shows this powerful network is hijacked to initiate breast cancer and fuel tumor growth, invasion and metastasis.

The team took a strain of mice that is highly resistant to breast cancer and then created four transgenic strains, each strain expressing one of the receptors or autotaxin.

At 24 months, none of the 44 original cancer-resistant mice developed mammary gland cancer. Only one case of inflammation and two cases of a potentially precancerous accumulation of cells known as hyperplasia were noted.

Cancer incidence ranged from 32 percent to 52.8 percent in the four strains of mice with one of the culprit receptors or autotaxin. Invasive and/or metastatic tumors were present to varying degrees, with 45.5 percent of the tumors in the LPA3 strain metastasizing.

A number of drugs are in preclinical development that target the receptors and autotaxin, Mills said. "Now we have transgenic mouse models to test drugs to go forward against these targets."

The four transgenic strains of mice have three unusual characteristics that the team believes make them particularly well-suited as a model of human breast cancer. Unlike most other mouse models, these produce breast cancer that is invasive and metastatic, and some tumors that are estrogen-receptor positive. ER-positive disease is the most common type of breast cancer.

The research was funded by grants from the National Cancer Institute, the U.S. Department of Defense Breast Cancer Research Program, the Breast Cancer Research Foundation, the M. D. Anderson NCI core grant, and sponsored research by LPATH Biotechnologies.

Co-authors are first author Shuying Liu, M.D., Ph.D., Makiko Umezu-Goto, Ph.D., Mandi Murph, Ph.D., Yiling Lu, M.D., Fan Zhang, M.S. and Shuangxing Yu, M.D., all of M. D. Anderson's Department of Systems Biology; Wenbin Liu, Ph.D. and Kevin Coombes, Ph.D., of the Department of Bioinformatics and Computational Biology; L. Clifton Stephens, Ph.D., D.V.M, of the Department of Veterinary Medicine and Surgery; and Mien-Chie Hung, Ph.D., Department of Molecular and Cellular Oncology; Adrian Lee, Ph.D., and Xiaojiang Cui, Ph.D., of the Lester and Sue Smith Breast Center at the Baylor College of Medicine, Cui is now with John Wayne Cancer Institute of Saint John's Health Center in Santa Monica, CA ; George Murrow and Charles Perou, Ph.D., of the Lineberger Comprehensive Cancer Center, University of North Carolina; William Muller, Ph.D., of McGill Cancer Centre in Montreal; and Xianjun Fang, Ph.D., of the Department of Biochemistry and Molecular Biology at Virginia Commonwealth University.

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 Repairing damaged hearts with self-healing heart cells
22.08.2017 | National University Health System

nachricht Biochemical 'fingerprints' reveal diabetes progression
22.08.2017 | Umea 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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Cholesterol-lowering drugs may fight infectious disease

22.08.2017 | Health and Medicine

Meter-sized single-crystal graphene growth becomes possible

22.08.2017 | Materials Sciences

Repairing damaged hearts with self-healing heart cells

22.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>