The researchers from the Garvan Institute of Medical Research in Sydney have found a new way of blocking signals to the molecule, stopping it from succeeding in its role of cell proliferation.

The molecule, known as Gab2, plays a part in the development of breast cancer along with the major breast cancer oncogene, HER2, the target of the drug Herceptin.

The researchers led by Professor Roger Daly, have been examining exactly how Gab2 functions, and how to stop it operating.

Professor Daly says Gab2 is a signalling protein, which is involved in transmitting signals from the cell surface to the interior of the cell, instructing it to do specific things, such as divide or migrate.

Professor Daly says Gab2 has a number of signalling roles in normal cells throughout the body, and is usually switched off when it's not needed and the team set out to discover how the body switches off Gab2 in order to mimic that process in abnormal cells.

Daly says they have identified a completely new mechanism for switching off Gab2 which uses another molecule that attaches to Gab2 and acts as a shield, preventing it from transmitting further proliferative signals.

The Professor says this 'off switch', is called 14-3-3, and is used to disable Gab2 in a number of cellular settings, when it is no longer needed.

He says as Gab2 plays key roles in signalling systems that underpin both normal physiological responses and oncogenesis, it's very important to understand its control mechanisms and the next step will be to obtain more structural information about how 14-3-3 shields Gab2.

Professor Daly says once that is known, it should be possible to design drugs to combat Gab2-activated diseases in new ways.

The finding is published online in the EMBO Journal.

The U.S. Institute of Medicine suggests that an adequate daily intake of vitamin D is between 200 and 400 international units (or blood levels nearing 30 nanograms per milliliter). Previous results from the same nationwide survey showed that 41 percent of men and 53 percent of women are technically deficient in the nutrient, with vitamin D levels below 28 nanograms per milliliter.

Michal Melamed, M.D., M.H.S., study co-lead investigator who started the research as a clinical fellow at Johns Hopkins, says no one knows yet why or how vitamin D's hormone-like properties may protect the heart, but she adds that there are plenty of leads in the better known links the vitamin has to problems with muscle overgrowth and high blood pressure, in addition to its control of inflammation, which scientists are showing plays a stronger role in all kinds of heart disease. But more research is needed to determine the nutrient's precise biological action.

Researchers say their next steps are to test various high doses of vitamin D to find out if the nutritional supplementation results in fewer deaths and lower incidence of heart disease, including heart attack or moments of prolonged and severe chest pain.

The team also plans to investigate what biological triggers, such as obesity or hypertension, might offset or worsen the action of vitamin D on heart muscle, or whether vitamin D sets off some other reaction in the heart.

Melamed says that because vitamin D levels are known to fluctuate in direct proportion with daily physical activity, the growing epidemic of obesity and indoor sedentary lifestyles lend more urgency to act on the vitamin D factor.

Funding for this study was provided by the National Institutes of Health, the P.J. Schafer Cardiovascular Research Fund and the Paul Beeson Physician Faculty Scholars in Aging Program. Michos has received previous consulting fees from vitamin D therapeutics manufacturer Abbott Pharmaceuticals. The terms of these arrangements are being managed by the Johns Hopkins University in accordance with its conflict of interest policies.

Besides Michos and Melamed, other Hopkins researchers involved in this study, conducted solely at Hopkins, were Wendy Post, M.D.; and Brad Astor, Ph.D. Melamed is now an assistant professor at the Albert Einstein College of Medicine of Yeshiva University in New York City.

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