1α,25-Dihydroxyvitamin D3 downregulates CYP27B1 and induces CYP24A1 in colon cells
1α,25-Dihydroxyvitamin D3 downregulates CYP27B1 and induces CYP24A1 in colon cells
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DOI：
10.1016/j.mce.2006.08.009
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发表时间：
2007-01-15
影响因子：
4.1
通讯作者：
Cross, Heide S.
中科院分区：
文献类型：
--
作者：
Lechner, Daniel;Kallay, Enikoe;Cross, Heide S.
抗有丝分裂和前分化的1 α，25-二羟维生素D-3（1 α，25-（OH）（2）D-3），在不同的肾外部位合成，可能会防止散发性肿瘤的发展。批次25（OH）（2）D-3组织蓄积后肾外维生素D羟化酶的生理调节尚不清楚。因此，我们研究了基础和维生素D调节的表达和活性的合成（CYP 27 B1）和代谢（CYP 24 A1）羟化酶在三个细胞系来自结肠，并比较这从前列腺和乳腺细胞。我们的研究结果表明，所有的细胞，无论起源和分化，表达CYP 27 B1 mRNA，而基础CYP 24 A1 mRNA仅在未分化的细胞中高度表达。用I α，25-（OH）（2）D-3处理降低了CYP 27 B1和维生素D受体mRNA的表达，但在所有细胞中将CYP 24 A1 mRNA升高至相同水平。如HPLC所示，仅当基础24-羟基化功能未达到最大时，CYP 27 B1才具有活性。反过来，批次25-（OH）（2）D-3的蓄积将诱导24-羟基化。我们的结论是，虽然维生素D的肾外和肾代谢途径是相似的，肿瘤细胞的恶性程度决定维生素D catalysts。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
The antimitotic and prodifferentiating 1 alpha,25-dihydroxyvitamin D-3(1 alpha,25-(OH)(2)D-3), synthesized at various extrarenal sites could potentially prevent sporadic tumor development. Physiological regulation of extrarenal Vitamin D hydroxylases following tissue accumulation of lot,25(OH)(2)D-3 is unknown. We therefore investigated basal and Vitamin D-regulated expression and activity of the synthesizing (CYP27B1) and metabolizing (CYP24A1) hydroxylase in three cell lines derived from the colon, and compared this to cells from the prostate and mammary gland. Our results show that all cells, irrespective of origin and differentiation, express CYP27B1 mRNA, whereas basal CYP24A1 mRNA is highly expressed only in undifferentiated cells. Treatment with I a,25-(OH)(2)D-3 diminishes CYP27B1 and Vitamin D receptor mRNA expression, but elevates CYP24A1 mRNA to equal levels in all cells. As shown by HPLC, CYP27B1 is active only if basal 24-hydroxylation is not maximally functional. In turn, accumulation of lot,25-(OH)(2)D-3 will induce 24-hydroxylation. We conclude that, although extrarenal and renal metabolic pathways for Vitamin D are similar, malignancy of tumor cells determines extent of Vitamin D catabolism. (c) 2006 Elsevier Ireland Ltd. All rights reserved.