Shinzato Amanda, Lerario Antonio M, Lin Chin J, Danilovic Debora S, Marui Suemi, Trarbach Ericka B
Laboratory of Cellular and Molecular Endocrinology, Hospital of the School of Medicine of São Paulo University (HCFMUSP), São Paulo, SP, Brazil.
Laboratory of Cardiovascular Pathology, Hospital of the School of Medicine of São Paulo University (HCFMUSP), São Paulo, SP, Brazil.
Med Sci Monit Basic Res. 2015 Aug 30;21:179-82. doi: 10.12659/MSMBR.895096.
BACKGROUND DREAM (Downstream Regulatory Element Antagonistic Modulator) is a neuronal calcium sensor that was suggested to modulate TSH receptor activity and whose overexpression provokes an enlargement of the thyroid gland in transgenic mice. The aim of this study was to investigate somatic mutations and DREAM gene expression in human multinodular goiter (MNG). MATERIAL AND METHODS DNA and RNA samples were obtained from hyperplastic thyroid glands of 60 patients (54 females) with benign MNG. DREAM mutations were evaluated by PCR and direct automatic sequencing, whereas relative quantification of mRNA was performed by real-time PCR. Over- and under-expression were defined as a 2-fold increase and decrease in comparison to normal thyroid tissue, respectively. RQ M (relative quantification mean); SD (standard deviation). RESULTS DREAM expression was detected in all nodules evaluated. DREAM mRNA was overexpressed in 31.7% of MNG (RQ M=6.26; SD=5.08), whereas 53.3% and 15% had either normal (RQ M=1.16; SD=0.46) or underexpression (RQ M=0.30; SD=0.10), respectively. Regarding DREAM mutations analysis, only previously described intronic polymorphisms were observed. CONCLUSIONS We report DREAM gene expression in the hyperplastic thyroid gland of MNG patients. However, DREAM expression did not vary significantly, and was somewhat underexpressed in most patients, suggesting that DREAM upregulation does not significantly affect nodular development in human goiter.
背景
DREAM(下游调节元件拮抗调节剂)是一种神经元钙传感器,有人认为它可调节促甲状腺激素受体活性,其过表达会导致转基因小鼠甲状腺肿大。本研究的目的是调查人类多结节性甲状腺肿(MNG)中的体细胞突变和DREAM基因表达。
材料与方法
从60例良性MNG患者(54例女性)的增生性甲状腺中获取DNA和RNA样本。通过PCR和直接自动测序评估DREAM突变,而mRNA的相对定量则通过实时PCR进行。过表达和低表达分别定义为与正常甲状腺组织相比增加和减少2倍。RQ M(相对定量平均值);SD(标准差)。
结果
在所有评估的结节中均检测到DREAM表达。31.7%的MNG中DREAM mRNA过表达(RQ M = 6.26;SD = 5.08),而53.3%和15%的患者分别为正常表达(RQ M = 1.16;SD = 0.46)或低表达(RQ M = 0.30;SD = 0.10)。关于DREAM突变分析,仅观察到先前描述的内含子多态性。
结论
我们报告了MNG患者增生性甲状腺中DREAM基因的表达。然而,DREAM表达没有显著变化,并且在大多数患者中略有低表达,这表明DREAM上调不会显著影响人类甲状腺肿的结节发育。