© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 6, 475-480,
March 15, 2000
© 2000 Oxford University Press
REPORTS |
Cellular Retinol-Binding Protein Expression and Breast Cancer
Affiliations of authors: Y. S. Kuppumbatti, S. Waxman, R. Mira-y-Lopez (Department of Medicine), I. J. Bleiweiss (Department of Pathology), J. P. Mandeli (Department of Biomathematical Sciences), Mount Sinai School of Medicine, New York, NY.
Correspondence to: Rafael Mira-y-Lopez, M.D., Ph.D., Department of Medicine, Mount Sinai School of Medicine, Box 1178, One Gustave L. Levy Place, New York, NY 10029-6574 (e-mail: mira{at}msvax.mssm.edu).
BACKGROUND: The biologic activity of vitamin A depends, in part, on its metabolism
to active nuclear receptor ligands, chiefly retinoic acid. The cellular retinol-binding
protein (CRBP) binds vitamin A with high affinity and is postulated to regulate its uptake and
metabolism. In this report, we analyze the expression of CRBP in normal and malignant breast
tissues. METHODS: We evaluated CRBP expression by in situ hybridization in
six reduction mammoplasty specimens and 49 human breast carcinoma specimens by use of
digoxigenin-labeled RNA probes and in nine cultured mammoplasty specimens by northern or
western blot analysis. Statistical significance was evaluated with the 
2 test or
Fisher's exact test if the sample sizes were small. All P values are from two-sided
tests. RESULTS: CRBP was expressed in all 15 mammoplasty specimens (normal breast
tissue) and in 33 of 35 available specimens of normal tissue adjacent to carcinoma. In contrast,
12 (24%) of 49 carcinoma lesions were uniformly negative for CRBP (P =
.023 for comparison with adjacent normal breast tissue). The loss of CRBP expression
was as frequent in ductal carcinoma in situ (six [27%] of 22) as in
invasive lesions (six [22%] of 27), suggesting that it is a relatively early event
in carcinogenesis and not associated with patient age, tumor grade, and expression of steroid
receptors or c-Myc. Preliminary experiments did not find an association between CRBP and
retinoic acid receptor ß loss, but most (four of five) CRBP-negative tumors were also
retinoic acid receptor ß negative. CONCLUSION: CRBP is underexpressed in
24% (95% confidence interval = 12.5%-36.5%) of human
breast carcinomas, implying a link between cellular vitamin A homeostasis and breast cancer.
We hypothesize that the loss of CRBP restricts the effects of endogenous vitamin A on breast
epithelial cells.
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