Pedrinola F, Rubio I, Santos C L, Medeiros-Neto G
Division of Endocrinology, University of São Paulo Medical School, Brazil.
Thyroid. 2001 Jan;11(1):15-20. doi: 10.1089/10507250150500612.
Thyroid malignancy has been induced by long-term endogenous thyrotropin (TSH) stimulation in experimental animals, leading to local and distant metastasis. It has been postulated that constant and prolonged endogenous TSH stimulation in dyshormonogenetic thyroid tissues could result in thyroid neoplasia. The possible role of growth factors and oncogenes in goitrogenesis and favoring neoplasia has also been mentioned. Overexpression of certain growth factors and/or their receptors, and of oncogenes implicated in growth promotion may play a significant role in the relatively frequent finding of thyroid malignancy in congenital goiters. In this study the expression of epidermal growth factor (EGF), epidermal growth factor receptor (EGF-R), transforming growth factor-beta (TGF-beta), c-myc, and p53 mRNAs was determined in 14 thyroid tissue samples: 6 from patients with thyroid peroxidase (TPO) gene mutations, 4 with thyroglobulin (Tg) gene defects and 4 normal thyroid tissues. EGF mRNA overexpression was seen in 7 of 10 dyshormonogenetic tissues (3.5 to 12.0 arbitrary optical densitometry units [AODU]) and considered significantly higher (p < 0.01) when compared to normal thyroid tissues (0.25 to 0.32 AODU). Moreover, overexpression of EGF-R mRNA was present in 6 of 10 dyshormonogenetic tissues (2.23 to 13.03 AODU) and considered significantly higher (p < 0.01) when compared to normal thyroid tissues (0.42 to 0.65 AODU). There was no difference in c-myc, p53, and TGF-beta mRNAs expression between dyshormonogenetic and normal tissues. The overexpression of EGF and EGF-R mRNAs found in dyshormonogenetic tissues may suggest that this growth factor may play a role in cellular proliferation and contribute to goiter formation.
在实验动物中，长期内源性促甲状腺激素（TSH）刺激可诱发甲状腺恶性肿瘤，并导致局部和远处转移。据推测，激素生成异常的甲状腺组织中持续且长期的内源性TSH刺激可能导致甲状腺肿瘤形成。生长因子和癌基因在甲状腺肿发生及肿瘤形成中的可能作用也已被提及。某些生长因子和/或其受体以及与生长促进相关的癌基因的过度表达，可能在先天性甲状腺肿中相对常见的甲状腺恶性肿瘤发生中起重要作用。在本研究中，测定了14份甲状腺组织样本中表皮生长因子（EGF）、表皮生长因子受体（EGF-R）、转化生长因子-β（TGF-β）、c-myc和p53 mRNA的表达：6份来自甲状腺过氧化物酶（TPO）基因突变患者，4份来自甲状腺球蛋白（Tg）基因缺陷患者，4份为正常甲状腺组织。在10份激素生成异常组织中的7份中可见EGF mRNA过度表达（3.5至12.0任意光密度测量单位[AODU]），与正常甲状腺组织（0.25至0.32 AODU）相比，被认为显著更高（p < 0.01）。此外，10份激素生成异常组织中的6份存在EGF-R mRNA过度表达（2.23至13.03 AODU），与正常甲状腺组织（0.42至0.65 AODU）相比，被认为显著更高（p < 0.01）。激素生成异常组织与正常组织之间的c-myc、p53和TGF-β mRNA表达无差异。在激素生成异常组织中发现的EGF和EGF-R mRNA过度表达可能表明该生长因子可能在细胞增殖中起作用并促进甲状腺肿形成。
