Zhalehjoo Naghmeh, Shakiba Yadollah, Panjehpour Mojtaba
Department of Clinical Biochemistry and Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan 81746‑73461, Iran.
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran 14176‑13151, Iran.
Mol Med Rep. 2017 Jan;15(1):467-473. doi: 10.3892/mmr.2016.5992. Epub 2016 Dec 6.
Active vitamin D has several antitumor effects, including prodifferentiative, antiproliferative and proapoptotic functions in a number of tissues via its binding to vitamin D receptor. The 24‑hydroxylase (CYP24A1) and 1‑hydroxylase (CYP27B1) enzymes are considered to be pivotal determinants of the local concentration of active vitamin D. The aim of the present study was to investigate the mRNA expression levels of the CYP24A1 and CYP27B1 genes in malignant and normal breast tissues. The tumor and adjacent normal tissue samples of 30 patients with breast cancer were acquired from the Iran National Tumor Bank, Imam Hospital (Tehran, Iran). RNA was extracted and, following cDNA synthesis, Taq‑Man quantitative polymerase chain reaction analysis was performed for CYP24A1 and CYP27B1. The results demonstrated that the mRNA expression of CYP27B1 was downregulated in the tumor tissues, compared with the adjacent normal tissues (P<0.01), whereas the mRNA expression of CYP24A1 was significantly upregulated in the tumor tissues (P<0.01). This major difference revealed that the normal breast tissues transcriptionally expressed CYP24A1 slightly. These results are suggestive of dysregulation of the vitamin D signaling and metabolic pathways during tumorigenesis in breast cancer. Local alterations in the anabolism and catabolism of active vitamin D in breast cancer by the CYP27B1 and CYP24A1 may impair its anticancer functions.
活性维生素D具有多种抗肿瘤作用,包括通过与维生素D受体结合,在许多组织中发挥促分化、抗增殖和促凋亡功能。24-羟化酶(CYP24A1)和1-羟化酶(CYP27B1)被认为是活性维生素D局部浓度的关键决定因素。本研究的目的是调查CYP24A1和CYP27B1基因在恶性和正常乳腺组织中的mRNA表达水平。从伊朗德黑兰伊玛目医院的伊朗国家肿瘤库获取了30例乳腺癌患者的肿瘤及相邻正常组织样本。提取RNA,在合成cDNA后,对CYP24A1和CYP27B1进行Taq-Man定量聚合酶链反应分析。结果表明,与相邻正常组织相比,肿瘤组织中CYP27B1的mRNA表达下调(P<0.01),而肿瘤组织中CYP24A1的mRNA表达显著上调(P<0.01)。这一主要差异表明正常乳腺组织中CYP24A1的转录表达轻微。这些结果提示在乳腺癌发生过程中维生素D信号和代谢途径失调。CYP27B1和CYP24A1对乳腺癌中活性维生素D合成代谢和分解代谢的局部改变可能会损害其抗癌功能。