Genomic vitamin D signaling in breast cancer: Insights from animal models and human cells.

Genomic vitamin D signaling in breast cancer: Insights from animal models and human cells.
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DOI:
10.1016/j.jsbmb.2010.03.061
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发表时间:
2010-07
影响因子:
4.1
通讯作者:
Welsh, JoEllen
Welsh, JoEllen
中科院分区:
生物学2区
文献类型:
--
作者:
Matthews, Donald;LaPorta, Erika;Zinser, Glendon M.;Narvaez, Carmen J.;Welsh, JoEllen

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这些研究的重点是确定影响乳腺癌发展或进展的维生素D调节途径。在小鼠实验中,我们评估了腺组织的基因组图谱,并从喂食足够(250 IU/kg)或高(5,000 IU/kg)维生素D(胆钙化醇)的MMTV-neu小鼠中建立肿瘤。基因组图谱也在差异表达VDR的鼠乳腺细胞中获得,所述细胞在体外与100 nM 1,25-二羟基维生素D(1,25 D)一起培养。在体外用1,25 D处理的小鼠细胞和高膳食维生素D喂养的小鼠乳腺中,鉴定了10个候选基因。在补充研究中,在人乳腺上皮细胞中评价了维生素D途径作为转化的函数。在人乳腺上皮细胞中,1,25 D调控的基因包括参与先天免疫(CD 14)、分化(Bmp 6)、细胞外基质重塑(Plau)和细胞存活(Birc 3)的基因。转化降低了VDR含量,并减弱了人乳腺细胞中1,25 D对一些但不是全部靶基因的诱导。总的来说,这些体内和体外数据表明,维生素D信号传导影响驱动分化、改变代谢、重塑细胞外基质和触发乳腺组织先天免疫的常见途径。
These studies focus on identification of vitamin D regulated pathways that impact development or progression of breast cancer. In mouse experiments, we assessed genomic profiles of glandular tissue and established tumors from MMTV-neu mice fed adequate (250 IU/kg) or high (5,000 IU/kg) vitamin D (cholecalciferol). Genomic profiles were also obtained in murine mammary cells that differentially express VDR that were cultured in vitro with 100nM 1,25-dihydroxyvitamin D (1,25D). Ten candidate genes were identified that were commonly regulated in murine cells treated with 1,25D in vitro and in mammary gland of mice fed high dietary vitamin D. In complementary studies, the vitamin D pathway was evaluated in human mammary epithelial cells as a function of transformation. Genes regulated by 1,25D in human mammary epithelial cells included those involved in innate immunity (CD14), differentiation (Bmp6), extracellular matrix remodeling (Plau) and cell survival (Birc3). Transformation reduced VDR content and blunted the induction of some, but not all, target genes by 1,25D in human mammary cells. Collectively, these in vivo and in vitro data demonstrate that vitamin D signaling impacts on common pathways that drive differentiation, alter metabolism, remodel the extracellular matrix and trigger innate immunity in mammary tissue.
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