Breast Cancer Discovery: Vitamin A Derivative Normalizes Cell Growth

What if a substance was found that normalizes out-of-control cell growth? The result could be a way to treat and prevent cancer. And a new study offers hope that discovery may have already been made. Scientists from the University of Chicago have just published groundbreaking research in the journal Cell which concludes a powerful compound exists that can restore a healthy balance to cell processes. It's not a new chemotherapy agent or drug but one derived from nature -- retinoic acid, a derivative of vitamin A

According to the American Cancer Society, estrogen fuels the growth of two out of three breast cancers. The female hormone can spur on cancer by altering the expression of certain genes, resulting in breast cells that become malignant and proliferate. The University of Chicago study found that retinoic acid can also alter these same estrogen-sensitive genes. But instead of causing cells to grow without restraint, a hallmark of cancer, retinoic acid restored normal balance to the cells and inhibited their growth. 

"This work reveals important insights on the interplay between vitamin A and estrogen action," said Myles Brown, MD, professor of medicine at Harvard Medical School and the Dana Farber Cancer Institute, in a statement to the media. "These insights will hopefully lead to new approaches for the prevention and treatment of the most common form of breast cancer."

Retinoic acid has already demonstrated cancer fighting effects in previous studies and it is currently used to treat a rare form of leukemia. In addition, earlier research has associated retinoic acid with the halting of breast cancer cell proliferation. 

For the new study, Kevin White, PhD, professor of human genetics and director of the Institute for Genomics and System Biology at the University of Chicago, and colleagues focused on documenting cell receptors for the vitamin A derivative. They used a process dubbed ChIP-chip analysis that combines chromatin immunoprecipitation (ChIP), which locates where the retinoic acid receptors are bound to the genome, with micro-array gene-chip analysis, which measures the expression levels of specific genes. 

This merging of techniques allowed the scientists to map out the complete genetic effects of retinoic acid and its receptors in a cell line provided by patients who had estrogen-fueled breast cancers. The results showed that 39 percent of the genomic regions bound by the estrogen receptor known as alpha overlapped with the estrogen receptors bound by retinoic acid.

What's more, they discovered that estrogen and retinoic acids receptors often competed to activate or repress many of the same genes. For example, estrogen increased expression of the same 139 genes that retinoic repressed and retinoic acid activated 185 genes that estrogen repressed. For approximately140 genes, estrogen and retinoic acid had the same effect.

So what does all this mean? As the scientists explained in their press statement, they now have evidence that estrogen and retinoic acid carry on a kind of "cross talk". So, although they can have opposite effects, certain estrogen and retinoic acid receptors on cells activate each other and normalize each other. That provides what the researchers call "an additional level of control for achieving a balanced regulation of expression."

The study also uncovered another way retinoic acid could help fight breast cancer. Some of the genes that are expressed in malignant breast tumors don't have estrogen receptors so anti-estrogen drugs can't be used as therapies. That makes so-called double or triple negative breast cancers extremely difficult to treat and, subsequently, they carry poor prognoses. However, in the new study, the researchers found these forms of cancerous cells did respond positively to the vitamin A derivative.

The new study may have produced a new way to help predict long-term survival for breast cancer patients, too. When the researchers compared the effects of retinoic acid on tissues from 295 breast cancer patients with the results from the scientists' initial study using a typical breast cancer cell line, they discovered that the more strongly a tumor responded to retinoic acid, the greater the chances of long-term survival and a lack of relapse.

"Understanding all the components of this process could be used against breast cancer in three ways," said Dr. White, in the media statement. "It suggests new ways to think about preventing the disease in those at high risk. It offers molecular tools that could provide a more precise diagnosis and predict outcomes. It could also be used to enhance current therapies, making existing drugs, such as tamoxifen, that selectively block estrogen's effects even more powerful, or even to develop new anti-cancer drugs."

As reported earlier in Natural News (http://www.naturalnews.com/025495_c...), researchers are also studying vitamin D to see what role it may play in fighting breast cancer. It appears to help protect against breast cancer by keeping normal cell growth in check.  (Natural News, 8.24.2009, S. L. Baker)
http://www.naturalnews.com/026901_cancer_brst_cancer_Retinoic_acid.html

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