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Pathways to Discovery: Fall 2012

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Vitamin D Receptor Suppresses Colon Cancer Growth

Vitamin D is traditionally recognized for its role in promoting calcium absorption and forming and maintaining strong bones. In recent years, research has suggested that vitamin D may play a role in preventing and treating a number of different conditions, including cancer. UCCCC researchers have been working toward understanding the mechanisms by which vitamin D suppresses cancer on cellular and molecular levels.

A paper published this past year in the International Journal of Cancer1 established a critical role for vitamin D in colon cancer growth. The research team, led by Associate Professor of Medicine Yan Chun Li, PhD, focused on a mutated molecular pathway implicated in colon cancer growth, adenomatous polyposis coli (APC)/ β-catenin, and its interaction with the vitamin D receptor (VDR), which mediates vitamin D activity.

Using mice genetically engineered to express the mutated signaling pathway, Dr. Li and colleagues compared tumor growth between groups expressing either normal VDR or inactivated VDR. They observed that the group with inactivated VDR grew significantly larger intestinal tumors. Laboratory analysis of these tumors also revealed higher protein levels of β-catenin, suggesting the APC/β-catenin pathway is more active without VDR.

“Our results suggest that the VDR’s signaling pathway suppresses colon cancer development,” said Dr. Li. The authors ascertained that VDR interfered with the APC/β- catenin signaling pathway by physically interacting with, and blocking the action of, β-catenin, based on in vitro studies using colon cancer cell cultures.

Future Studies
Through collaboration with Marc Bissonnette, MD, associate professor of medicine, Dr. Li is developing another preclinical study to determine if vitamin D supplementation can reduce the growth of colon tumors in mice. In a parallel clinical study, the team is evaluating whether 6 months of 2,000-4,000 international units of daily vitamin D supplementation will prevent colon polyps from recurring in African American patients. Among all racial and ethnic groups, African Americans not only experience the highest incidence and mortality rates from colorectal cancer, but they also have the lowest levels of serum vitamin D.

On a larger scale, a randomized, multicenter clinical trial2 has been underway in North America since 2004 to study the effects of vitamin D supplementation on new polyp growth in patients who previously had cancerous polyps removed. Dr. Li anticipates that the preliminary results, which should be available in April 2014, will reveal whether vitamin D supplementation can significantly suppress colon cancer.

The Sunshine Vitamin
Epidemiological data suggest that environmental factors, such as exposure to sunlight, may play an important role in determining colon cancer risk. For instance, epidemiologists have observed that populations living in northern regions with less sun exposure have higher rates of colon cancer than populations living in sunnier climates. Exposure to sunlight activates vitamin D synthesis in the skin.

“Our study offers an explanation for why vitamin D suppresses colon cancer and also why it is important for people to maintain their body’s vitamin D level,” said Dr. Li.

1This research study was supported in part by grant numbers T32 DK07074 and R03 CA117472 from the National Institutes of Health.
2This research study was supported in part by grant number CA098286 from the National Institutes of Health.

Ernst Lengyel