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 Scientists enlist engineered protein to battle the MERS virus
22.05.2017 | University of Toronto

nachricht Insight into enzyme's 3-D structure could cut biofuel costs
19.05.2017 | DOE/Los Alamos National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

Im Focus: Hydrogen Bonds Directly Detected for the First Time

For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.

Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

Media accreditation opens for historic year at European Health Forum Gastein

16.05.2017 | Event News

 
Latest News

New approach to revolutionize the production of molecular hydrogen

22.05.2017 | Materials Sciences

Scientists enlist engineered protein to battle the MERS virus

22.05.2017 | Life Sciences

Experts explain origins of topographic relief on Earth, Mars and Titan

22.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>