The samples of breast tissue are analyzed for signs of atypia, including a critical alteration to RAR beta in which the gene is silenced by methylation. Methylation is thought to be triggered by environmental factors such as diet, nutrition, smoking and chemical exposures. These environmental triggers prompt a group of molecules to attach to a gene and convey a message to silence or reduce its expression. The gene itself remains unchanged, which is why scientists can't search for a mutation in the gene.
Seewaldt describes methylation as like putting gum on a light switch. The light isn't broken, but it can't be switched on.
When RAR beta isn't turned on, it can't signal two other important tumor suppressor genes -- CBP and p300 -- which are also critical in regulating how a cell grows.
One key to reversing the methylation of RAR beta could lie in vitamin A and substances similar to vitamin A, said Seewaldt. Her recent studies have shown that vitamin A can actually demethylate RAR beta. In doing so, vitamin A initiates an important feedback loop that suppresses tumor growth in this way:
Vitamin A turns on the RAR beta gene
The RAR beta gene expresses a protein called a receptor
The receptor acts like a dock that receives messages from hormones, vitamins, and the environment and conveys them inside the cell
the messages are transmitted to CBP and p300
CBP and p300 express their own proteins that enable the cell to better utilize vitamin A for its tumor-suppressing activities.
Seewaldt likens the process to a relay race. If one first runner doesn't connect with the next runner, the entire loop is broken.
"We've always known that vitamins are important in the prevention of cancer, but here is a clear-cut example at the cellular level demonstrating that normal amounts of fresh vegetables -- leafy greens, carrots, sweet potatoes -- may be very important in p
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Contact: Becky Levine
levin005@mc.duke.edu
919-684-4148
Duke University Medical Center
4-Mar-2004