GENE-EXPRESSION OF DIFFERENTIATION MARKERS AND DEDIFFERENTIATION MARKERS IN NORMAL AND MALIGNANT HUMAN THYROID TISSUES
GENE-EXPRESSION OF DIFFERENTIATION MARKERS AND DEDIFFERENTIATION MARKERS IN NORMAL AND MALIGNANT HUMAN THYROID TISSUES
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DOI：
10.1055/s-0029-1211176
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发表时间：
1992-01-01
期刊：
影响因子：
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通讯作者：
BRABANT, G
中科院分区：
文献类型：
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作者：
HOANGVU, C;DRALLE, H;BRABANT, G
用北方印迹分析法研究了甲状腺肿瘤患者和正常对照者甲状腺分化标志物如TSH受体（TSHR）、甲状腺球蛋白（Tg）和甲状腺过氧化物酶（TPO）以及潜在的去分化标志物c-myc标志物的稳态mRNA转录水平。通过吖啶橙子染色使印迹标准化，而β-肌动蛋白mRNA水平的分析揭示了在正常组织中已经存在的高度可变的水平，表明该“组成型”表达基因的调节。c-myc mRNA的测定显示，与正常组织相比，间变性癌（ATC）中的稳态mRNA水平增加。然而，在一些患者中，c-myc转录水平低于肿瘤比在邻近的正常组织中降低c-myc作为去分化的标志物的意义。高水平的TSH mRNA被发现在控制甲状腺，而在ATC没有正常的TSHR mRNA被检测到。在PTC和滤泡性甲状腺癌（FTC）中，转录本的水平从增加到显着降低不等。在1例FTC 2患者中，肿瘤的独立制备物显示了不同的结果，无法检测到和可清楚检测到TSHR mRNA水平。该组织在裸鼠上的异种移植在个体异种移植中显示出可变的表达模式，表明肿瘤组织的异质性。Tg和TPO mRNA在正常组织中强表达，在所有ATC中完全缺失。在分化型甲状腺肿瘤中，Tg和TPO的转录水平从正常到Tg或TPO或两者表达完全丧失不等。甲状腺分化标志物表达的这种变化可能反映了肿瘤相同组织学形态中细胞内信号转导途径的变化，其模式可能最终导致肿瘤的不同分类。
Steady state mRNA transcript levels of thyroid differentiation markers such as TSH receptor (TSHR), thyroglobulin (Tg) and thyroid peroxidase (TPO) as well as a potential marker of dedifferentiation, c-myc, marker were investigated in patients with thyroid tumors and in normal controls using Northern blot analysis. Blots were normalized by acridine orange staining whereas analysis of beta-actin mRNA levels revealed highly variable levels already in normal tissue suggesting regulation of this "constitutively" expressed gene. Determination of c-myc mRNA revealed increased steady state mRNA levels in anaplastic carcinomas (ATC) as compared to normal tissues. However, in some patients c-myc transcript levels were lower in the tumor than in the adjacent normal tissue reducing the significance of c-myc as a marker of dedifferentiation.High levels of TSH mRNA were found in control thyroids, whereas in ATC no normal TSHR mRNA was detected. In PTC and follicular thyroid carcinomas (FTC) the transcripts varied from increased to markedly reduced levels. In one patient with FTC 2 independant preparations of the tumor revealed different results, undetectable and clearly detectabe TSHR mRNA levels. Xenotransplantation of this tissue on nude rats showed a variable expression pattern in the individual xenotransplantations suggesting heterogeneity of the tumor tissue. Tg and TPO mRNA were strongly expressed in normal tissues and completely lost in all ATC. In differentiated thyroid tumors the transcript levels of Tg and TPO varied from normal to complete loss of expression of either Tg or TPO, or both. This variability of the expression of thyroid differentiation markers may reflect variable alterations of the intracellular signal transduction pathways in the tumors identical histological morphology and their pattern may eventually lead to a different classification of the tumors.