Conde I, Paniagua R, Fraile B, Ruiz A, Arenas M I
Department of Cell Biology and Genetics, University of Alcalá, 28871 Alcalá de Henares, Madrid, Spain.
Int J Oncol. 2004 Oct;25(4):1183-91.
Vitamin D3 (VD) and all-trans-retinoic acid (ATRA) have been postulated as a novel treatment option for breast carcinoma. Since the combined effects of retinoids and VD derivatives are attributed to heterodimeric interactions between members of the nuclear receptor family, the expression patterns of the heterodimers formed by vitamin D3 receptor (VDR) and the retinoid receptors RARs (RAR-alpha, RAR-beta and RAR-gamma) and RXRs (RXR-alpha, RXR-beta and RXR-gamma) have been studied by immunohistochemistry in benign and malignant breast tissues. Present results revealed that immunoexpressions to all receptor types studied were higher in both in situ and infiltrative carcinomas than in benign breast diseases. In a variable number of cases of infiltrative carcinoma, immunostaining appeared in the nucleus, whereas in the other two disorders immunostaining was only cytoplasmic. The correlation established between VDR and the different isoforms of retinoid receptors revealed that VDR seems to select mainly RAR-alpha to form heterodimers and to exert their properties as transcription factor. The results of this study suggest that this heterodimer plays a critical role in cancer malignancy, and its presence indicates those patient groups presenting a better response to adjuvant therapies based on the combination of vitamin D and ATRA.
维生素D3（VD）和全反式维甲酸（ATRA）已被假定为乳腺癌的一种新型治疗选择。由于类视黄醇和VD衍生物的联合作用归因于核受体家族成员之间的异二聚体相互作用，因此通过免疫组织化学研究了维生素D3受体（VDR）与类视黄醇受体RARs（RAR-α、RAR-β和RAR-γ）以及RXRs（RXR-α、RXR-β和RXR-γ）形成的异二聚体在良性和恶性乳腺组织中的表达模式。目前的结果显示，所研究的所有受体类型的免疫表达在原位癌和浸润性癌中均高于良性乳腺疾病。在不同数量的浸润性癌病例中，免疫染色出现在细胞核中，而在其他两种疾病中免疫染色仅出现在细胞质中。VDR与类视黄醇受体不同亚型之间建立的相关性表明，VDR似乎主要选择RAR-α形成异二聚体并发挥其作为转录因子的特性。本研究结果表明，这种异二聚体在癌症恶性肿瘤中起关键作用，其存在表明那些对基于维生素D和ATRA联合的辅助治疗反应较好的患者群体。
