Cellular retinol-binding protein expression and breast cancer
| Autor: | Rafael Mira-y-Lopez, Samuel Waxman, John Mandeli, Yuvarani S. Kuppumbatti, Ira J. Bleiweiss |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cancer Research
medicine.medical_specialty DNA Complementary Receptors Retinoic Acid Mammaplasty Retinoic acid Genes myc Retinoic acid receptor beta Breast Neoplasms Tretinoin In situ hybridization Biology medicine.disease_cause chemistry.chemical_compound Breast cancer Internal medicine Carcinoma medicine Humans Breast RNA Neoplasm Vitamin A In Situ Hybridization Carcinoma Ductal Breast Retinol Retinol-Binding Proteins Cellular Ductal carcinoma medicine.disease Blotting Northern Gene Expression Regulation Neoplastic Retinol-Binding Proteins Endocrinology Oncology chemistry Cancer research Female Carcinogenesis Carcinoma in Situ Signal Transduction |
| Zdroj: | Journal of the National Cancer Institute. 92(6) |
| ISSN: | 0027-8874 |
| Popis: | 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 chi(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 beta loss, but most (four of five) CRBP-negative tumors were also retinoic acid receptor beta 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. |
| Databáze: | OpenAIRE |
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