Role of COX-2, thromboxane A2 synthase, and prostaglandin I2 synthase in papillary thyroid carcinoma growth
Role of COX-2, thromboxane A2 synthase, and prostaglandin I2 synthase in papillary thyroid carcinoma growth
复制标题
DOI：
10.1038/modpathol.3800285
复制
发表时间：
2005-02-01
期刊：
影响因子：
7.5
通讯作者：
Lloyd, RV
中科院分区：
文献类型：
--
作者：
Kajita, S;Ruebel, KH;Lloyd, RV
甲状腺乳头状癌的发展受到许多因素的影响，包括遗传改变、生长因子和物理因素（例如辐射）。花生四烯酸及其衍生物，包括前列腺素 (PG) 和血栓素以及参与其合成的酶已被证明可以影响各种肿瘤的生长。我们通过 RT-PCR 分析了乳头状癌和匹配正常组织中环氧合酶-2 (COX-2) 的免疫反应性以及 COX-2、血栓素 A(2) (TXA(2)) 合酶和 PGI(2) 合酶的 mRNA 表达水平，以确定这些酶在乳头状甲状腺癌发展中的作用。还对甲状腺乳头状癌细胞系 TPC-1 进行了体外研究，以确定特异性 COX-2 抑制剂 NS-398 对 COX-2 和血管内皮生长因子-A 的作用，因为 COX-2 也具有调节肿瘤血管生成的作用。 RT-PCR 分析显示，与正常甲状腺组织相比，甲状腺乳头状癌中 TXA2 合酶 mRNA 水平显着升高。尽管乳头状癌中COX-2 mRNA水平普遍升高，但差异无统计学意义。 PGI(2)合酶mRNA水平没有显着差异。与正常甲状腺组织相比，乳头状癌中COX-2蛋白表达更高；然而，水平差异很大。 COX-2 抑制剂 NS-398 的体外研究显示，肿瘤生长受到抑制，同时 COX-2 和血管内皮生长因子-A mRNA 表达水平增加。这些结果表明，PG 合成途径中的特定酶（如 TXA(2) 合酶）水平在甲状腺乳头状癌中增加。 COX-2 在甲状腺乳头状生长中也发挥作用，因为 COX-2 的特异性抑制剂可调节甲状腺乳头状癌细胞的增殖。这些结果暗示前列腺素合成中的几种酶作为甲状腺乳头状癌增殖的调节剂，并表明这些酶表达水平的增加可能在这些肿瘤的发病机制中发挥作用。
The development of papillary thyroid carcinoma is influenced by many factors including genetic alterations, growth factors, and physical agents such as radiation. Arachidonic acid and its derivatives including prostaglandins ( PG) and thromboxane along with the enzymes involved in their synthesis have been shown to influence the growth of various tumors. We analyzed the immunoreactivity for cyclooxygenase-2 (COX-2) and mRNA expression levels of the enzymes COX-2, thromboxane A(2) (TXA(2)) synthase, and PGI(2) synthase by RT-PCR in papillary carcinomas and matching normal tissues to determine the role of these enzymes in the development of papillary thyroid carcinomas. A papillary thyroid carcinoma cell line TPC-1 was also studied in vitro to determine the role of the specific COX-2 inhibitor NS-398 on COX-2 and vascular endothelial growth factor-A, since COX- 2 also has a role in regulating tumor angiogenesis. RT-PCR analysis showed significant increases in TXA2 synthase mRNA levels in papillary thyroid carcinomas compared to normal thyroid tissues. Although COX- 2 mRNA levels were generally increased in papillary carcinomas, the differences were not statistically significant. There were no significant differences in PGI(2) synthase mRNA levels. COX- 2 protein expression was greater in papillary carcinoma compared to normal thyroid tissues; however, the levels were quite variable. In vitro studies with a COX- 2 inhibitor, NS-398, showed inhibition of tumor growth along with increased levels of COX- 2 and vascular endothelial growth factor-A mRNA expression. These results indicate that specific enzyme levels in the PG synthesis pathway such as TXA(2) synthase are increased in papillary thyroid carcinomas. COX- 2 also has a role in papillary thyroid growth, since a specific inhibitor of COX- 2 regulates papillary thyroid carcinoma cell proliferation. These results implicate several enzymes in the synthesis of prostanoids as regulators of thyroid papillary carcinoma proliferation and suggest that increased levels of expression of these enzymes may play a role in the pathogenesis of these tumors.