Wang D G, Liu W H, Lundy F T, Pogue K M, Cunningham R T, Johnston C F, Buchanan K D
Department of Medicine, School of Clinical Medicine, Queen's University of Belfast, U.K.
J Pathol. 1998 Apr;184(4):408-13. doi: 10.1002/(SICI)1096-9896(199804)184:4<408::AID-PATH1222>3.0.CO;2-3.
Medullary thyroid carcinoma (MTC) is an uncommon tumour of calcitonin-secreting C-cells of the thyroid gland. This cancer represents an important potential model for the study of mechanisms of human epithelial cell transformation. Although recent studies have identified the gene involved in familial forms of MTC, little is known about the molecular pathogenesis of the sporadic variants of this tumour. The biological and prognostic significance of TFF1 expression, particularly in diverse human malignancies, suggests that the TFF1 protein could have a role in human neoplasia. Furthermore, in prostate cancer it has been demonstrated that TFF1 expression is closely associated with premalignant changes and neuroendocrine differentiation. In the present study, the expression of TFF1 was analysed in 18 human MTCs, comprising sporadic and familial tumours, C-cell hyperplasia, and one case of lymph gland metastasis. TFF1 expression was also examined in the cultures of a human MTC-derived tumour cell line (TT cell line). The results showed that ten sporadic tumours, three hereditary tumours (including C-cell hyperplasia), and one lymph gland metastasis displayed TFF1 immunoreactivity. Indirect fluorescence immunocytochemistry and Western blotting revealed that the TFF1 protein was strongly expressed in the TT cells. Northern analysis revealed that tumours and TT cells expressed the TFF1 transcript. Although the function of TFF1 protein in the carcinogenesis of MTC remains to be elucidated, its expression in the majority of cases of both sporadic and hereditary tumours, metastatic tumours, and in C-cell hyperplasia suggests that it may contribute to the pathogenesis of MTC.
甲状腺髓样癌（MTC）是一种由甲状腺分泌降钙素的C细胞发生的罕见肿瘤。这种癌症是研究人类上皮细胞转化机制的重要潜在模型。尽管最近的研究已经确定了与家族性MTC相关的基因，但对于该肿瘤散发性变体的分子发病机制知之甚少。TFF1表达的生物学和预后意义，特别是在多种人类恶性肿瘤中的意义，表明TFF1蛋白可能在人类肿瘤形成中发挥作用。此外，在前列腺癌中已经证明，TFF1表达与癌前变化和神经内分泌分化密切相关。在本研究中，分析了18例人类MTC中的TFF1表达，包括散发性和家族性肿瘤、C细胞增生以及1例淋巴结转移。还在人MTC来源的肿瘤细胞系（TT细胞系）培养物中检测了TFF1表达。结果显示，10例散发性肿瘤、3例遗传性肿瘤（包括C细胞增生）和1例淋巴结转移呈现TFF1免疫反应性。间接荧光免疫细胞化学和蛋白质印迹显示，TFF1蛋白在TT细胞中强烈表达。Northern分析显示，肿瘤和TT细胞表达TFF1转录本。尽管TFF1蛋白在MTC致癌作用中的功能尚待阐明，但其在大多数散发性和遗传性肿瘤、转移性肿瘤以及C细胞增生病例中的表达表明，它可能参与了MTC的发病机制。
