The impact of vitamin D in breast cancer: genomics, pathways, metabolism.
The impact of vitamin D in breast cancer: genomics, pathways, metabolism.
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DOI：
10.3389/fphys.2014.00213
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发表时间：
2014
影响因子：
4
通讯作者：
Welsh J
中科院分区：
文献类型：
--
作者：
Narvaez CJ;Matthews D;LaPorta E;Simmons KM;Beaudin S;Welsh J
核受体对乳腺生理学产生深远影响，并在乳腺癌的病因学中发挥复杂的作用。除了雌激素和黄体酮等经典类固醇激素的受体外，核维生素 D 受体 (VDR) 与其配体 1α,25(OH)2D3 相互作用，调节正常乳腺上皮细胞基因组和随后的表型。观察性研究表明，维生素 D 缺乏症在乳腺癌患者中很常见，而维生素 D 水平较低会增加疾病发生或进展的风险。基因组分析已经表征了正常乳腺细胞和乳腺癌中许多 1α,25(OH)2D3 响应靶标，从而深入了解 1α,25(OH)2D3 和 VDR 在调节细胞周期、凋亡和分化中的分子作用。新的重点领域包括肿瘤代谢和先天免疫反应的调节。然而，VDR 在正常和肿瘤组织的单个细胞类型（即上皮细胞、脂肪细胞、成纤维细胞、内皮细胞、免疫细胞）中的作用仍有待阐明。此外，VDR 整合不同细胞类型之间的信号传导并控制组织/肿瘤微环境中的可溶性信号和旁分泌途径的机制仍有待确定。致癌模型系统提供的证据表明，VDR 表达和 1α,25(OH)2D3 作用均随转化而变化，但有关已建立肿瘤的维生素 D 反应性的临床数据有限且不确定。由于乳腺癌具有异质性，因此分析 VDR 在该疾病特定分子亚型中的作用可能有助于澄清相互矛盾的数据。基因组学、蛋白质组学和代谢组学方法在各种体外和体内模型系统上的广泛使用显然有必要全面了解乳腺癌背景下维生素 D 调节途径的网络。
Nuclear receptors exert profound effects on mammary gland physiology and have complex roles in the etiology of breast cancer. In addition to receptors for classic steroid hormones such as estrogen and progesterone, the nuclear vitamin D receptor (VDR) interacts with its ligand 1α,25(OH)2D3 to modulate the normal mammary epithelial cell genome and subsequent phenotype. Observational studies suggest that vitamin D deficiency is common in breast cancer patients and that low vitamin D status enhances the risk for disease development or progression. Genomic profiling has characterized many 1α,25(OH)2D3 responsive targets in normal mammary cells and in breast cancers, providing insight into the molecular actions of 1α,25(OH)2D3 and the VDR in regulation of cell cycle, apoptosis, and differentiation. New areas of emphasis include regulation of tumor metabolism and innate immune responses. However, the role of VDR in individual cell types (i.e., epithelial, adipose, fibroblast, endothelial, immune) of normal and tumor tissues remains to be clarified. Furthermore, the mechanisms by which VDR integrates signaling between diverse cell types and controls soluble signals and paracrine pathways in the tissue/tumor microenvironment remain to be defined. Model systems of carcinogenesis have provided evidence that both VDR expression and 1α,25(OH)2D3 actions change with transformation but clinical data regarding vitamin D responsiveness of established tumors is limited and inconclusive. Because breast cancer is heterogeneous, analysis of VDR actions in specific molecular subtypes of the disease may help to clarify the conflicting data. The expanded use of genomic, proteomic and metabolomic approaches on a diverse array of in vitro and in vivo model systems is clearly warranted to comprehensively understand the network of vitamin D regulated pathways in the context of breast cancer.
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影响因子：
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