Isolation and characterization of a pituitary tumor-transforming gene (PTTG).
Isolation and characterization of a pituitary tumor-transforming gene (PTTG).
复制标题
DOI：
10.1210/mend.11.4.9911
复制
发表时间：
1997-04
影响因子：
--
通讯作者：
L. Pei;S. Melmed
中科院分区：
文献类型：
--
作者：
L. Pei;S. Melmed
垂体前叶肿瘤形成的发病机制已被深入研究，但涉及垂体细胞转化和肿瘤发生的共同机制仍不清楚。在这项研究中，我们使用mRNA差异显示PCR来鉴定大鼠垂体瘤细胞与正常垂体组织相比差异表达的mRNA。一种mRNA仅在垂体瘤中表达，而在正常垂体中不表达。以该垂体瘤特异性PCR产物为探针，从大鼠垂体瘤GH4细胞构建的cDNA文库中筛选出一个974 bp的cDNA。该cDNA编码一种新的199个氨基酸的蛋白质，其不包含充分表征的功能基序。该cDNA的mRNA在正常成人睾丸和胚胎肝中检测到，其中转录物短约300 bp，并且表达水平比从垂体瘤细胞中检测到的低得多。该蛋白在小鼠3T3成纤维细胞中的过表达表明其抑制细胞增殖并诱导体外细胞转化。将转染的3T3细胞注射到无胸腺裸鼠中导致所有动物在3周内形成肿瘤。这些结果表明，垂体瘤细胞表达一个独特的和有效的转化基因（PTTG），这可能在垂体肿瘤的发生中发挥作用。
Pathogenesis of tumor formation in the anterior pituitary has been intensively studied, but the common mechanism involved in pituitary cell transformation and tumorigenesis remains elusive. In this study, we used mRNA differential display PCR to identify mRNAs that are differentially expressed in rat pituitary tumor cells compared with normal pituitary tissue. An mRNA exclusively expressed in pituitary tumor but not in normal pituitary was characterized. Using this pituitary tumor-specific PCR product as a probe to screen a cDNA library constructed from rat pituitary tumor GH4 cells, a cDNA of 974 bp was isolated. This cDNA encodes a novel protein of 199 amino acids, which contains no well characterized functional motifs. The mRNA of this cDNA is detected in normal adult testis and in embryonic liver, where the transcript is about 300 bp shorter and expressed at a much lower level than that detected from pituitary tumor cells. Overexpression of this protein in mouse 3T3 fibroblasts shows that it inhibits cell proliferation and induces cell transformation in vitro. Injection of transfected 3T3 cells into athymic nude mice resulted in tumor formation within 3 weeks in all animals. These results indicate that pituitary tumor cells express a unique and potent transforming gene (PTTG), which may play a role in pituitary tumorigenesis.