PAX8-PPARγ1 fusion in oncogene human thyroid carcinoma
PAX8-PPARγ1 fusion in oncogene human thyroid carcinoma
复制标题
DOI：
10.1126/science.289.5483.1357
复制
发表时间：
2000-08-25
期刊：
影响因子：
56.9
通讯作者：
Fletcher, JA
中科院分区：
文献类型：
--
作者：
Kroll, TG;Sarraf, P;Fletcher, JA
在白血病/淋巴瘤和肉瘤中一致观察到编码融合癌蛋白的染色体易位，但在最常见的人类癌症癌中却没有观察到。在这里，我们报道了 t(2;3)(q13;p25)，一种在人类甲状腺滤泡癌亚群中发现的易位，导致甲状腺转录因子 PAX8 的 DNA 结合域与过氧化物酶体增殖物激活受体 (PPAR) gamma 1 的 A 至 F 域融合。PAX8-PPAR gamma 1 mRNA 和蛋白质是 在 8 例甲状腺滤泡性癌中的 5 例中检测到，但在 20 例滤泡性腺瘤、10 例乳头状癌或 10 例多结节性增生中未检测到。 PAX8-PPAR gamma 1 以显性负向方式抑制 PPAR gamma 1 噻唑烷二酮诱导的反式激活。实验证明了 PPAR gamma 的致癌作用，并表明 PAX8-PPAR gamma 1 可能有助于甲状腺癌的诊断和治疗。
Chromosomal translocations that encode fusion oncoproteins have been observed consistently in leukemias/lymphomas and sarcomas but not in carcinomas, the most common human cancers. Here, we report that t(2;3)(q13;p25), a translocation identified in a subset of human thyroid follicular carcinomas, results in fusion of the DNA binding domains of the thyroid transcription factor PAX8 to domains A to F of the peroxisome proliferator-activated receptor (PPAR) gamma 1. PAX8-PPAR gamma 1 mRNA and protein were detected in 5 of 8 thyroid follicular carcinomas but not in 20 follicular adenomas, 10 papillary carcinomas, or 10 multinodular hyperplasias. PAX8-PPAR gamma 1 inhibited thiazolidinedione-induced transactivation by PPAR gamma 1 in a dominant negative manner. The experiments demonstrate an oncogenic role for PPAR gamma and suggest that PAX8-PPAR gamma 1 may be useful in the diagnosis and treatment of thyroid carcinoma.