Diesing Dagmar, Cordes Tim, Fischer Dorothea, Diedrich Klaus, Friedrich Michael
University of Schleswig-Holstein, Department of Gynaecology and Obstetrics, 23627 Luebeck, Germany.
Anticancer Res. 2006 Jul-Aug;26(4A):2755-9.
The three main vitamin D metabolizing enzymes, vitamin D3-25-hydroxylase (25-OHase, 25-hydroxylase), 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-OHase, 1alpha-hydroxylase) and 25-hydroxyvitamin D3-24-hydroxylase (24-OHase, 24-hydroxylase), have been described in malignant breast tissue. This in vitro study aimed to obtain more information regarding the regulation of these enzymes in the human breast cancer cell line MCF-7.
Vitamin D receptor (VDR)- positive MCF-7 cells in culture were stimulated with the vitamin D metabolites vitamin D3, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 for 24, 48; 72 and 96 hours in physiological and supraphysiological concentrations. The expressions of 25-hydroxylase, 1alpha-hydroxylase and 24-hydroxylase and their changes after stimulation were assessed by real-time PCR.
The expression of 25-hydroxylase was slightly influenced by vitamin D3. The expression of 1alpha-hydroxylase was induced after stimulation with vitamin D3 and 25-hydroxyvitamin D3. Stimulation with 1,25-dihydroxyvitamin D3 markedly increased the expression of 24-hydroxylase time- and dose-dependently.
Our results demonstrated that MCF-7 cells are able to regulate the expression of 24-hydroxylase. This might be a mechanism for these tumor cells to protect themselves against the antiproliferative and apoptosis-inducing effects of calcitriol.
三种主要的维生素D代谢酶,即维生素D3 - 25 - 羟化酶(25 - OHase,25 - 羟化酶)、25 - 羟基维生素D3 - 1α - 羟化酶(1α - OHase,1α - 羟化酶)和25 - 羟基维生素D3 - 24 - 羟化酶(24 - OHase,24 - 羟化酶),已在恶性乳腺组织中被描述。这项体外研究旨在获取更多关于这些酶在人乳腺癌细胞系MCF - 7中调节机制的信息。
培养的维生素D受体(VDR)阳性MCF - 7细胞用维生素D代谢物维生素D3、25 - 羟基维生素D3和1,25 - 二羟基维生素D3在生理和超生理浓度下刺激24、48、72和96小时。通过实时PCR评估25 - 羟化酶、1α - 羟化酶和24 - 羟化酶的表达及其刺激后的变化。
25 - 羟化酶的表达受维生素D3的影响较小。维生素D3和25 - 羟基维生素D3刺激后可诱导1α - 羟化酶的表达。1,25 - 二羟基维生素D3刺激可显著地、呈时间和剂量依赖性地增加24 - 羟化酶的表达。
我们的结果表明MCF - 7细胞能够调节24 - 羟化酶的表达。这可能是这些肿瘤细胞保护自身免受骨化三醇抗增殖和诱导凋亡作用的一种机制。