Mammary adipocytes bioactivate 25-hydroxyvitamin D₃ and signal via vitamin D₃ receptor, modulating mammary epithelial cell growth.
Mammary adipocytes bioactivate 25-hydroxyvitamin D₃ and signal via vitamin D₃ receptor, modulating mammary epithelial cell growth.
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DOI：
10.1002/jcb.23273
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发表时间：
2011-11
影响因子：
4
通讯作者：
Zinser, Glendon M.
中科院分区：
文献类型：
--
作者：
Ching, Stephen;Kashinkunti, Soumya;Niehaus, Matthew D.;Zinser, Glendon M.
维生素D3受体（VDR）存在于乳腺的所有微环境中，但据推测是通过上皮细胞发出信号来调节激素诱导的生长和分化。然而，乳腺内表达VDR的其他微环境（如乳腺脂肪组织）的影响或作用尚未得到研究。我们假设乳腺脂肪细胞表达参与维生素D3合成以及通过VDR进行信号传导所必需的信号成分，从而调节导管上皮细胞的生长和分化。我们利用人原代乳腺脂肪细胞以及VDR野生型（WT）和敲除型（KO）小鼠来研究乳腺脂肪细胞是否参与维生素D3诱导的导管上皮生长调节。我们在本研究中报道，乳腺原代脂肪细胞表达VDR、CYP27B1（1α - 羟化酶，1α - OHase，该酶可产生具有生物活性的VDR配体1α,25 - 二羟基维生素D3（1,25D3））以及CYP24（24 - 羟化酶，24 - OHase，一种VDR - 1,25D3诱导的靶基因）。此外，乳腺脂肪细胞参与将25 - 羟基维生素D3（25D3）生物活化为活性配体1,25D3，并将其分泌到周围微环境中。为支持这一概念，我们报道从VDR敲除型小鼠中纯化的乳腺导管上皮片段（类器官）与野生型乳腺脂肪细胞共培养时，与单独使用溶媒相比，用25D3或1,25D3处理后其生长受到抑制。总之，这些结果表明乳腺脂肪细胞将25D3生物活化为1,25D3，通过脂肪细胞内的VDR发出信号，并释放一种调节导管上皮细胞生长的抑制因子，这表明乳腺脂肪组织有助于维生素D3诱导的导管上皮生长调节。
The Vitamin D3 Receptor (VDR) is present in all microenvironments of the breast, yet is hypothesized to signal through the epithelium to regulate hormone induced growth and differentiation. However, the influence or contribution of the other microenvironments within the breast that express VDR, like the breast adipose tissue, have yet to be investigated. We hypothesized that the breast adipocytes express the signaling components necessary to participate in vitamin D3 synthesis and signaling via VDR, modulating ductal epithelial cell growth and differentiation. We utilized human primary breast adipocytes and VDR wild type (WT) and knockout (KO) mice to address whether breast adipocytes participate in vitamin D3-induced growth regulation of the ductal epithelium. We report in this study that breast primary adipocytes express VDR, CYP27B1 (1α-hydroxylase, 1α-OHase), the enzyme that generates the biologically active VDR ligand, 1α,25-dihydroxyvitamin D3 (1,25D3), and CYP24 (24- hydroxylase, 24-OHase), a VDR-1,25D3 induced target gene. Furthermore, the breast adipocytes participate in bioactivating 25-hydroxyvitamin D3 (25D3) to the active ligand, 1,25D3, and secreting it to the surrounding microenvironment. In support of this concept, we report that purified mammary ductal epithelial fragments (organoids) from VDR KO mice, co-cultured with WT breast adipocytes, were growth inhibited upon treatment with 25D3 or 1,25D3 compared to vehicle alone. Collectively, these results demonstrate that breast adipocytes bioactivate 25D3 to 1,25D3, signal via VDR within the adipocytes, and release an inhibitory factor that regulates ductal epithelial cell growth, suggesting that breast adipose tissue contributes to vitamin D3-induced growth regulation of ductal epithelium.
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DOI：
10.1016/j.jsbmb.2008.09.006
发表时间：
2008-11
影响因子：
4.1
作者：
Li, Jia;Byrne, Mary E.;Chang, Eugene;Jiang, Yan;Donkin, Shawn S.;Buhman, Kimberly K.;Burgess, John R.;Teegarden, Dorothy
通讯作者：
Teegarden, Dorothy
影响因子：
--
作者：
Hovey, RC;Goldhar, AS;Vonderhaar, BK
通讯作者：
Vonderhaar, BK
DOI：
10.1016/s0006-291x(88)80482-0
发表时间：
1988-03-30
影响因子：
3.1
作者：
ISHIDA, Y;TANIGUCHI, H;BABA, S
通讯作者：
BABA, S
影响因子：
3.8
作者：
Kleinberg, DL
通讯作者：
Kleinberg, DL
影响因子：
2.5
作者：
Couldrey, C;Moitra, J;Green, J
通讯作者：
Green, J