The Candidate Oncogene CYP24A1: A Potential Biomarker for Colorectal Tumorigenesis
The Candidate Oncogene CYP24A1: A Potential Biomarker for Colorectal Tumorigenesis
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DOI：
10.1369/jhc.2009.954339
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发表时间：
2010-03-01
影响因子：
3.2
通讯作者：
Kallay, Enikoe
中科院分区：
文献类型：
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作者：
Horvath, Henrik C.;Lakatos, Peter;Kallay, Enikoe
维生素 D-3 活性代谢物 1 α,25-二羟基维生素 D-3 (1,25-D-3) 的主要自分泌/旁分泌作用是抑制细胞生长并诱导细胞分化和/或凋亡。分泌类固醇的合成和降解不仅发生在肾脏中，而且发生在正常组织或恶性肾外组织如结肠中。由于 25-羟基维生素 D-3 24-羟化酶 (CYP24A1) 被认为是决定 1,25-D-3 生物半衰期的主要酶，因此我们检测了 CYP24A1 mRNA（通过实时 RT-PCR）和蛋白质（通过免疫组织化学）在正常人结肠粘膜、结直肠腺瘤和结肠癌中的表达。 111 名患者患有腺癌。尽管 76% 的正常和良性结肠组织完全不含 CYP24A1 或表达水平非常低，但在大多数腺癌 (69%) 中，该酶以高浓度存在。同一样本中增殖标志物 Ki-67 的表达平行增加表明 CYP24A1 的过度表达降低了局部 1,25-D-3 的可用性，从而降低了其抗增殖作用。 (J Histochem Cytochem 58:277-285, 2010)
The main autocrine/paracrine role of the active metabolite of vitamin D-3, 1 alpha,25-dihydroxyvitamin D-3 (1,25-D-3), is inhibition of cell growth and induction of cell differentiation and/or apoptosis. Synthesis and degradation of the secosteroid occurs not only in the kidney but also in normal tissue or malignant extrarenal tissues such as the colon. Because 25-hydroxyvitamin D-3 24-hydroxylase (CYP24A1) is considered to be the main enzyme determining the biological half-life of 1,25-D-3, we have examined expression of the CYP24A1 mRNA (by real-time RT-PCR) and protein (by immunohistochemistry) in normal human colon mucosa, colorectal adenomas, and adenocarcinomas in 111 patients. Although 76% of the normal and benign colonic tissue was either completely devoid of or expressed very low levels of CYP24A1, in the majority of the adenocarcinomas (69%), the enzyme was present at high concentrations. A parallel increased expression of the proliferation marker Ki-67 in the same samples suggests that overexpression of CYP24A1 reduced local 1,25-D-3 availability, decreasing its antiproliferative effect. (J Histochem Cytochem 58:277-285, 2010)