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维生素D受体表达与人类甲状腺乳头状癌的潜在标志物相关。

Vitamin D receptor expression is linked to potential markers of human thyroid papillary carcinoma.

作者信息

Izkhakov Elena, Somjen Dalia, Sharon Orli, Knoll Esther, Aizic Asaf, Fliss Dan M, Limor Rona, Stern Naftali

机构信息

Institute of Endocrinology, Metabolism and Hypertension, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Institute of Endocrinology, Metabolism and Hypertension, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

出版信息

J Steroid Biochem Mol Biol. 2016 May;159:26-30. doi: 10.1016/j.jsbmb.2016.02.016. Epub 2016 Feb 22.

Abstract

Genes regulated cell-cell and cell-matrix adhesion and degradation of the extracellular matrix (ECM) have been screened as potential markers of malignant thyroid nodules. The mRNA expression levels of two of them, the ECM protein-1 (ECM1) and the type II transmembrane serine protease-4 (TMPRSS4), were shown to be an independent predictor of an existing thyroid carcinoma. The vitamin D receptor (VDR) is expressed in epithelial cells of the normal thyroid gland, as well as in malignant dividing cells, which respond to the active metabolite of vitamin D by decreased proliferative activity in vitro. We evaluated the relationship between mRNA gene expressions of TMPRSS4, ECM1 and VDR in 21 papillary thyroid carcinoma samples and compared it to 21 normal thyroid tissues from the same patients. Gene expression was considered as up- or down-regulated if it varied by more or less than 2-fold in the cancer tissue relative to the normal thyroid tissue (Ca/N) from the same patient. We found an overall significant adjusted correlation between the mRNA expression ratio (ExR) of VDR and that of ECM1 in Ca/N thyroid tissue (R=0.648, P<0.001). There was a high ExR of VDR between Ca/N thyroid tissue from the same patient (3.06±2.9), which also exhibited a high Ca/N ExR of ECM1 and/or of TMPRSS4 (>2, P=0.05).The finding that increased VDR expression in human thyroid cancer cells is often linked to increased ECM1 and/or TPMRSS4 expression warrants further investigation into the potential role of vitamin D analogs in thyroid carcinoma.

摘要

已筛选出调控细胞间和细胞与细胞外基质(ECM)黏附及ECM降解的基因作为甲状腺恶性结节的潜在标志物。其中两种基因,即ECM蛋白-1(ECM1)和II型跨膜丝氨酸蛋白酶-4(TMPRSS4)的mRNA表达水平被证明是现存甲状腺癌的独立预测指标。维生素D受体(VDR)在正常甲状腺的上皮细胞以及恶性分裂细胞中均有表达,这些细胞在体外对维生素D的活性代谢产物作出反应,表现为增殖活性降低。我们评估了21例甲状腺乳头状癌样本中TMPRSS4、ECM1和VDR的mRNA基因表达之间的关系,并将其与同一患者的21例正常甲状腺组织进行比较。如果癌组织中基因表达相对于同一患者的正常甲状腺组织(Ca/N)变化超过或低于2倍,则认为基因表达上调或下调。我们发现,在Ca/N甲状腺组织中,VDR与ECM1的mRNA表达比值(ExR)之间存在总体显著的校正相关性(R = 0.648,P < 0.001)。同一患者的Ca/N甲状腺组织之间VDR的ExR较高(3.06±2.9),同时ECM1和/或TMPRSS4的Ca/N ExR也较高(>2,P = 0.05)。人类甲状腺癌细胞中VDR表达增加常与ECM1和/或TPMRSS4表达增加相关,这一发现值得进一步研究维生素D类似物在甲状腺癌中的潜在作用。

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