"We are the first to demonstrate the requirement for beta1-integrin in the induction breast cancer in genetically engineered mice, " says senior author Dr. William Muller, a MUHC researcher and professor of Medicine and Biochemistry at McGill University. "Our findings show that blocking the function of this gene halts tumour proliferation. We also show that in our model of breast cancer, tumour cells do not grow without beta1-intergrin. These results demonstrate the importance of this gene in tumour biology. The next step is to look for therapeutics which block this gene in humans."

Dr. Muller and his colleagues from the Department of Biochemistry and Biomedical Sciences at McMaster University, Dr. John Hassel, Natasza Kurpios and Don White, used breast-cancer prone mice to demonstrate the role of beta1-integrin. They initially showed that removing this gene did not effect the normal mammary development of the mice. They then went on to show that if this gene was removed from already growing tumours, the tumours would cease to grow.

"This is an exciting time in breast cancer research," says McMaster University and McGill University graduate student and first author of the study, Don White. "The more players we identify, the more likely we are to cure this disease."

These findings are published in the August 23, issue of Cancer Cell and are currently available online at cancercell

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Little is known about the NPAS1 and NPAS3 genes. Both genes are expressed in brain cells called inhibitory interneurons. These neurons are smaller than the typical excitatory neurons, which pass electrical signals amongst themselves and act as the brain ™s wiring. The role of inhibitory interneurons, on the other hand, is to dampen the activity of excitatory neurons.

The NPAS1 and NPAS3 proteins are transcription factors that can activate or deactivate other genes. Just which genes they may control is unclear, Dr. McKnight said.

Dr. McKnight and his research team are currently investigating what genes and what kind of brain cells the NPAS1 and NPAS3 proteins are acting upon. Information about this particular chemical pathway could provide further clues to a genetic link with human psychosis.

Other UT Southwestern biochemistry researchers involved in the study were first authors Drs. Claudia Erbel-Sieler and Xinle Wu, both postdoctoral researchers, and Carol Dudley, senior research scientist; Sandi Jo Estill, research assistant, and Tina Han, research technician. Dr. Ramon Diaz-Arrastia, associate professor of neurology at UT Southwestern and researchers from the University of Mississippi, the University of Cincinnati Medical School and the Children ™s Medical Center in Cincinnati also participated.

The research was supported, in part, by the National Institute of Mental Health, the McKnight Foundation for Neuroscience and the Morton H. Meyerson Tzedukah Fund.

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