Vitamin D and Breast Cancer: Mechanistic Update.
Vitamin D and Breast Cancer: Mechanistic Update.
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作者：
Welsh J
维生素D受体（VDR）在乳腺和乳腺癌中的存在早已被认识到，多项临床前研究已经证明其配体1,25‐二羟基维生素D （1,25D）在动物模型中调节正常乳腺发育并抑制乳腺肿瘤的生长。维生素D缺乏在乳腺癌患者中很常见，一些证据表明，维生素D水平低会增加疾病发展或进展的风险。虽然在正常乳腺细胞和乳腺癌中已经发现了许多1,25 d应答靶点，但对调节细胞周期、凋亡、自噬和分化的特定靶点的验证，特别是在体内，一直具有挑战性。癌变模型系统提供的证据表明，VDR表达和1,25D的作用都随着转化而改变，但关于已建立肿瘤的维生素D反应性的临床数据有限且不确定。由于乳腺癌是异质性的，相关的VDR靶点和对维生素D补充或补充的潜在敏感性可能会因患者群体而异。有必要详细分析VDR在疾病特定分子亚型中的作用，以澄清相互矛盾的数据。体外和体内模型系统的基因组学、蛋白质组学和代谢组学分析也有必要全面了解乳腺癌异质性背景下维生素d调节通路的网络。这篇综述提供了最近关于维生素D在乳腺癌中的作用的机制（细胞/分子）、临床前（动物模型）和转化工作的最新研究。©2021作者。JBMR Plus由Wiley期刊有限责任公司代表美国骨骼和矿物研究协会出版。
The presence of the vitamin D receptor (VDR) in mammary gland and breast cancer has long been recognized, and multiple preclinical studies have demonstrated that its ligand, 1,25‐dihydroxyvitamin D (1,25D), modulates normal mammary gland development and inhibits growth of breast tumors in animal models. Vitamin D deficiency is common in breast cancer patients, and some evidence suggests that low vitamin D status enhances the risk for disease development or progression. Although many 1,25D‐responsive targets in normal mammary cells and in breast cancers have been identified, validation of specific targets that regulate cell cycle, apoptosis, autophagy, and differentiation, particularly in vivo, has been challenging. Model systems of carcinogenesis have provided evidence that both VDR expression and 1,25D actions change with transformation, but clinical data regarding vitamin D responsiveness of established tumors is limited and inconclusive. Because breast cancer is heterogeneous, the relevant VDR targets and potential sensitivity to vitamin D repletion or supplementation will likely differ between patient populations. Detailed analysis of VDR actions in specific molecular subtypes of the disease will be necessary to clarify the conflicting data. Genomic, proteomic, and metabolomic analyses of in vitro and in vivo model systems are also warranted to comprehensively understand the network of vitamin D–regulated pathways in the context of breast cancer heterogeneity. This review provides an update on recent studies spanning the spectrum of mechanistic (cell/molecular), preclinical (animal models), and translational work on the role of vitamin D in breast cancer. © 2021 The Author. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.