OBJECTIVES The study was designed to evaluate expression profiling of mitogen-activated protein kinase (MAPK) signalling pathway genes in sporadic parathyroid adenoma. METHODS Expression of MAPK signalling pathway genes including activated transcription factors and cell cycle regulatory genes was analysed by real-time PCR- based array in parathyroid adenoma (N = 20) and normal parathyroid tissue (N = 4). RESULTS MAPK signalling pathway as studied by PCR array revealed that a total of 22 genes were differentially expressed (≥ twofold change, p ≤ 0.05) in parathyroid adenoma. Up-regulated genes were ARAF, MAPK12, CREBBP, MYC, HSPB1, HRAS, CDK4, CCND1, and E2F1, and down-regulated genes were MAP4K1, DLK1, MAP3K4, MAPK10, MAPK8, ATF2, SMAD4, MEF2C, LAMTOR3, FOS, CDKN2A CDKN2B, and RB1. The present study revealed that ERK1/2 signalling pathway with up-regulation of HRAS, ARAF, and MEK1 genes and up-regulation of positive regulators of cell cycle (CCND1, CDK4, and E2F1) and down-regulation negative regulators of cell cycle (CDKN2A, CDKN2B, and RB1) made highly dysregulated MAPK signalling pathway in parathyroid adenoma. Expression of CDK4 was positively associated with plasma PTH level (r = 0.60, p = 0.04) and tumor weight (r = 0.80, p = 0.02) of the adenoma patients, respectively. Expression of CDKN2A was correlated negatively with PTH level (r = - 0.52, p = 0.04) of the adenoma patients. CONCLUSION The current study revealed that ERK pathway and associated cell cycle regulator genes are dysregulated in sporadic parathyroid adenoma.

中文翻译：

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散发性甲状旁腺肿瘤中失调的有丝分裂原激活的蛋白激酶途径介导的细胞周期破坏。

目的本研究旨在评估散发性甲状旁腺腺瘤中有丝分裂原活化蛋白激酶（MAPK）信号通路基因的表达谱。方法采用实时荧光定量PCR技术分析甲状旁腺腺瘤（N = 20）和正常甲状旁腺组织（M = 4）中MAPK信号通路基因（包括活化的转录因子和细胞周期调控基因）的表达。结果通过PCR阵列研究的MAPK信号通路显示，共有22个基因在甲状旁腺腺瘤中差异表达（≥两倍变化，p≤0.05）。上调的基因是ARAF，MAPK12，CREBBP，MYC，HSPB1，HRAS，CDK4，CCND1和E2F1，而下调的基因是MAP4K1，DLK1，MAP3K4，MAPK10，MAPK8，ATF2，SMAD4，MEF2C，LAMTOR3，FOS， CDKN2A CDKN2B和RB1。本研究揭示了ERK1 / 2信号通路与HRAS，ARAF和MEK1基因的上调以及细胞周期的正调控因子（CCND1，CDK4和E2F1）的上调以及细胞周期的负调控因子的下调（ CDKN2A，CDKN2B和RB1）使甲状旁腺腺瘤中的MAPK信号通路高度失调。CDK4的表达分别与腺瘤患者血浆PTH水平（r = 0.60，p = 0.04）和肿瘤重量（r = 0.80，p = 0.02）正相关。CDKN2A的表达与腺瘤患者的PTH水平呈负相关（r =-0.52，p = 0.04）。结论当前的研究表明散发性甲状旁腺腺瘤中ERK通路和相关的细胞周期调节基因失调。和MEK1基因以及细胞周期正调控因子（CCND1，CDK4和E2F1）的上调和细胞周期负调控因子（CDKN2A，CDKN2B和RB1）的下调使得甲状旁腺腺瘤中的MAPK信号通路高度失调。CDK4的表达分别与腺瘤患者血浆PTH水平（r = 0.60，p = 0.04）和肿瘤重量（r = 0.80，p = 0.02）正相关。CDKN2A的表达与腺瘤患者的PTH水平呈负相关（r =-0.52，p = 0.04）。结论当前的研究表明散发性甲状旁腺腺瘤中ERK通路和相关的细胞周期调节基因失调。和MEK1基因以及细胞周期正调控因子（CCND1，CDK4和E2F1）的上调和细胞周期负调控因子（CDKN2A，CDKN2B和RB1）的下调使得甲状旁腺腺瘤中的MAPK信号通路高度失调。CDK4的表达分别与腺瘤患者血浆PTH水平（r = 0.60，p = 0.04）和肿瘤重量（r = 0.80，p = 0.02）正相关。CDKN2A的表达与腺瘤患者的PTH水平呈负相关（r =-0.52，p = 0.04）。结论当前的研究表明散发性甲状旁腺腺瘤中ERK通路和相关的细胞周期调节基因失调。CDK4的表达分别与腺瘤患者血浆PTH水平（r = 0.60，p = 0.04）和肿瘤重量（r = 0.80，p = 0.02）正相关。CDKN2A的表达与腺瘤患者的PTH水平呈负相关（r =-0.52，p = 0.04）。结论当前的研究表明散发性甲状旁腺腺瘤中ERK通路和相关的细胞周期调节基因失调。CDK4的表达分别与腺瘤患者血浆PTH水平（r = 0.60，p = 0.04）和肿瘤重量（r = 0.80，p = 0.02）正相关。CDKN2A的表达与腺瘤患者的PTH水平呈负相关（r =-0.52，p = 0.04）。结论当前的研究表明散发性甲状旁腺腺瘤中ERK通路和相关的细胞周期调节基因失调。