A new study shows that the loss of a cellular protein involved in vitamin A metabolism occurs in some breast cancers. The authors suggest that this loss diminishes the beneficial effects of vitamin A on normal breast cells.
Yuvarani S. Kuppumbatti, Ph.D., Rafael Mira-y-Lopez, M.D., Ph.D., and colleagues at the Mount Sinai School of Medicine, New York, present these findings in the March 15 issue of the Journal of the National Cancer Institute.
Vitamin A is required for the maintenance of normal epithelial cell differentiation. The biologic activity of vitamin A depends, in part, on its metabolism to retinoic acid. The cellular retinol-binding proteinCRBPbinds vitamin A with high affinity and is thought to regulate its uptake and metabolism. This activity of CRBP led the authors to measure CRBP in normal and malignant breast tissues. They worked with 15 specimens from women who had undergone breast reduction surgery and 49 breast cancer tissue specimens. Thirty-five of the cancer specimens contained normal breast tissue adjacent to the cancer that could also be probed for CRBP. The cancer specimens, the adjacent normal tissue, and the six breast-reduction tissues were analyzed by in situ hybridization, and the nine cell cultures from breast-reduction specimens were analyzed by northern or western blot analysis.
CRBP was found in all 15 samples from breast-reduction surgery and was present in 33 of the 35 specimens of normal tissue that were adjacent to cancerous tissue. In contrast, 12 (24%) of the 49 cancer tissues were uniformly negative for CRBP. The loss of CRBP was found as frequently in ductal carcinoma in situ (an early, noninvasive type of breast cancer) as in invasive cancers, suggesting that the loss is a relatively early event in the development of cancer. The loss of CRBP was not associated with patient age, steroid receptor status, lymph node status, tumor grade, or other factors.
The authors conclude that CRBP expression is frequently lost in breast cancer. They speculate that loss of CRBP would be expected to compromise vitamin A uptake and metabolism within cells, thus providing a growth advantage to cancer cells.
In an editorial, Michael Spinella, Ph.D., and Ethan Dmitrovsky, M.D., Dartmouth Medical School, Hanover, NH, note that vitamin A and its derivatives have activity in cancer therapy and prevention. These include the treatment of premalignant lesions, the reduction of second cancers of the head and neck, lung, and liver, as well as the treatment of some leukemias and other cancers. The discovery of the nuclear retinoid receptors in the 1980s revolutionized the retinoid field by providing a firm mechanistic basis for understanding the cellular actions of retinoids. The editorial writers note that the study by Kuppumbatti et al. is important because it identifies a tumor-associated abnormality in a protein linked to retinoid metabolism. However, they add that a critical question is whether loss of CRBP is associated with altered retinoid levels within these breast tumors. Furthermore, because of the small sample size and minority of cases having loss of CRBP in the study by Kuppumbatti et al., Spinella and Dmitrovsky stress the need for confirmatory studies.
Contact: Debra Kaplan, Mount Sinai, (212) 659-9045; fax: (212) 803-6772. Editorial: Hali Wicker, Dartmouth, (603) 650-1520; fax: (603) 650-1730.
Note: This memo to reporters is from the Journal staff and is not an official release of the National Cancer Institute (NCI) or Oxford University Press (OUP) nor does it reflect NCI or OUP policy. In addition, unless otherwise stated, all articles and items published in the Journal reflect the individual views of the authors and not necessarily the official points of view held by NCI, any other component of the U.S. government, OUP, or the organizations with which the authors are affiliated. Neither NCI nor any other component of the U.S. government nor OUP assumes any responsibility for the completeness of the articles or other items or the accuracy of the conclusions reached therein.
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