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Study Examines Relationship of Vitamin A Pathway to Breast Cancer Tumor Progression
JNCI ^ | 01.05.05

Posted on 01/19/2005 8:14:48 PM PST by Coleus

It has long been suspected that vitamin A may be linked to cancer prevention. The mechanisms by which this may be happening, however, have yet to be understood. Conversely, scientists have discovered that a malfunction in the way the body processes vitamin A may be the culprit behind the formation of breast cancer.

Vitamin A, or retinol, can be found in a number of food products, such as cod liver oil, milk, eggs and fruits and vegetables; however, too much vitamin A can be toxic to the body.

Vitamin A Processing

  • Once the vitamin enters the body, it is stored in the liver and other tissues, including the breast

  • When it is needed, the vitamin is converted into retinoic acid, activating the retinoic acid receptor in the cells

  • The receptor regulates the expression of a variety of genes, most of which are associated with cell differentiation

  • When cell differentiation occurs, the genes turn into cells with specific roles to play; cells that don't differentiate can develop into tumors

If the cells don't get enough vitamin A stored, the retinoic acid receptor doesn't get activated, cells don't differentiate and they can turn cancerous.

Through working with human and mouse breast cells, scientists found that the problem stemmed from the cellular retinol-binding protein I (CRBP-I), which is involved in the process of storing the vitamin. One scientist added, "We found that, in the early stages of tumor formation, if you don't have CRBP or LRAT [another protein] to store the retinol, it's likely the receptors will not work in a normal way. This means that cells can't differentiate, and therefore start to proliferate into tumors."

Journal of the National Cancer Institute January 5, 2005;97(1):1

Study Examines Relationship of Vitamin A Pathway to Breast Tumor Progression

Sarah L. Zielinski
Journal of the National Cancer Institute

Reduced expression of a protein that regulates the metabolism of vitamin A may contribute to tumor progression in breast cancer, according to a new study in the January 5 issue of the Journal of the National Cancer Institute. The study raises the possibility that this vitamin A pathway is a potential target for breast cancer prevention.

Defects in vitamin A, or retinol, bioactivity may be a possible contributor to human carcinogenesis because vitamin A is required for activation of the retinoic acid receptor (RAR), which induces differentiation of adult epithelial cells. One of the characteristics of epithelial cancers is the loss of differentiated attributes. It has been hypothesized that vitamin A bioactivity in cancer cells may be compromised at the level of retinol metabolism, which is regulated by a number of proteins, including cellular retinol-binding protein I (CRBP-I). A study of CRBP-I in mice demonstrated that the protein plays an essential role in vitamin A storage. In addition, CRBP-I expression is down-regulated in about a quarter of human breast cancers. However, it is not known if reduced CRBP-I function compromises vitamin A bioactivity and, if so, whether such a reduction in function would lead to a loss of differentiation and tumor progression.

To determine whether there is a link between retinol storage, RAR activation, and CRBP-I function in the development of breast cancer, Eduardo F. Farias, Ph.D., of Mount Sinai School of Medicine in New York, and colleagues studied RAR activity, retinol storage, CRBP-I localization, and cell differentiation in human and mouse mammary epithelial cells—which can be used as a model of breast cancer—that expressed normal or mutant CRBP-I.

They found that, in the cells, RAR activation was dependent on CRBP-I-mediated retinol storage, and downregulation of CRBP-I compromised RAR activity, leading to loss of cell differentiation and tumor progression. The authors also observed that the breast tumors derived from these cells that expressed normal CRBP-I regressed, whereas those that did not express CRBP-I continued to grow.

"Our in vivo data suggest that somatic CRBP-I loss of function results in a local deficit in vitamin A storage and metabolism that has profound consequences for the affected tissue, despite presumably normal circulating levels of vitamin A," the authors write. "The consequence of deficient vitamin A storage is a fundamental point that needs to be studied further, but if CRBP-I is indeed essential..., then epidemiologic studies attempting to correlate human vitamin A status with cancer incidence may have been partly misguided."

In an editorial, Reuben Lotan, M.D., of the University of Texas M. D. Anderson Cancer Center in Houston, discusses the role of retinoids in normal development and suggests future research strategies to determine how retinoids may prevent tumor formation and growth of both hormone receptor-positive and -negative breast cancers.




TOPICS: Health/Medicine; Science
KEYWORDS: breastcancer; cancer; nutrition; supplements; vitamina; vitamins
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1 posted on 01/19/2005 8:14:49 PM PST by Coleus
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