Vitamin A linked to breast cancer
10 January 2005

Researchers have found a link between impaired storage of vitamin A in cells and the development and progression of breast cancer.

Although preliminary, the team hopes the findings may lead to new drug targets for preventing breast cancer and other malignancies. In the meantime, however, Dr Eduardo Farias (Mount Sinai School of Medicine, New York, USA) and colleagues warn against consuming large amounts of vitamin A, which can be toxic to the body.

Once taken into the body, vitamin A is stored in the liver and other tissues, including the breast. When needed, it is converted into retinoic acid, which then activates the retinoic acid receptor (RAR) in cells. In turn, this activation regulates the operation of genes, most of which are associated with turning general cells into those with specific roles. Cells that do not differentiate correctly can turn into tumour cells.

Previous research has shown that stores of retinal are low in the breast tissue of cancer patients, irrespective of whether or not the individual is consuming adequate amounts of vitamin A in their diet.

Noting that if cells do not have enough vitamin A stored they will not differentiate and so may turn cancerous, Dr Farias and colleagues looked at the process by which this may occur.

They found that the problem stemmed from a deficiency in a protein called cellular retinol-binding protein (CRBP)-I, which is involved in the storage of retinol. In cells, activation of the RAR was dependent on this CRBP-1, and so reduced levels of the protein led to compromised RAR activity, preventing cells from differentiating. This left cells more susceptible to being changed into tumour cells.

Moreover, the researchers found that if CRBP-1 was added to cells lacking the protein this prevented the progression of tumour cells.

The authors write in the Journal of the National Cancer Institute that their data suggest that loss of function in CRBP-1 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." Thus, the design of therapies targeting the gene that produces CRBP-1 may be one area for future research, together with drugs that could restore levels of the protein, they add.