The RET/PTC3 oncogene: metastatic solid-type papillary carcinomas in murine thyroids.
The RET/PTC3 oncogene: metastatic solid-type papillary carcinomas in murine thyroids.
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发表时间：
1998-12
期刊：
影响因子：
11.2
通讯作者：
D. Powell;John C. Russell;K. Nibu;Guoqi Li;E. Rhee;M. Liao;Michael R. Goldstein;W. Keane;M. Santoro;A. Fusco;J. Rothstein
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文献类型：
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作者：
D. Powell;John C. Russell;K. Nibu;Guoqi Li;E. Rhee;M. Liao;Michael R. Goldstein;W. Keane;M. Santoro;A. Fusco;J. Rothstein
我们的研究目标是更好地了解控制甲状腺疾病发生和发展的机制。其中一种疾病，乳头状甲状腺癌（PTC），是美国最主要的内分泌恶性肿瘤。最近，一个家族的相关融合蛋白，RET/PTC 1 -5，已牵连在PTC的早期阶段。虽然这个家族的所有五个成员在其COOH末端都有c-RET原癌基因激酶结构域，但对这些基因如何改变滤泡细胞生物学知之甚少。因此，为了回答与RET/PTC融合蛋白作用机制相关的问题，我们设计了一种分子遗传学策略来使用甲状腺疾病小鼠模型研究PTC。在我们的研究中，研究了这个融合癌基因家族的新成员RET/PTC 3，它与实体瘤癌的病例数（79%）比PTC 1或PTC 2更多，并且在儿童放射诱导的甲状腺癌中占主导地位（80%）。我们已经产生了只在甲状腺中表达人RET/PTC 3的转基因小鼠。这些小鼠发生甲状腺增生、乳头状癌的实体瘤变体和转移性癌症。这一新的转基因品系将有助于解释导致人类PTC和组织学变异的分子和生物学机制。
Our research goal is to better understand the mechanisms controlling the initiation and progression of thyroid diseases. One such disease, papillary thyroid carcinoma (PTC), is the leading endocrine malignancy in the United States. Recently, a family of related fusion proteins, RET/PTC1-5, has been implicated in the early stages of PTC. Although all five members of this family have the c-RET proto-oncogene kinase domain in their COOH terminus, little is known about how these genes alter follicular cell biology. Consequently, to answer questions related to the mechanism of the RET/PTC fusion protein action, we have devised a molecular genetic strategy to study PTC using a mouse model of thyroid disease. A new member of this fusion oncogene family, RET/PTC3, which has been implicated in more cases of solid tumor carcinoma (79%) than PTC1 or PTC2 and predominates (80%) in radiation-induced thyroid cancer of children, was investigated in our study. We have generated transgenic mice expressing human RET/PTC3 exclusively in the thyroid. These mice develop thyroid hyperplasia, solid tumor variants of papillary carcinoma and metastatic cancer. This new transgenic line will be useful in deciphering the molecular and biological mechanisms that cause PTC and histological variations in humans.