Structure, expression, and function of human pituitary tumor-transforming gene (PTTG)

被引:274
作者
Zhang, X
Horwitz, GA
Prezant, TR
Valentini, A
Nakashima, M
Bronstein, MD
Melmed, S
机构
[1] Univ Calif Los Angeles, Sch Med, Cedars Sinai Res Inst, Los Angeles, CA 90048 USA
[2] Univ Sao Paulo, Sch Med, Div Funct Neurosurg, Neuroendocrine Unit, BR-01406100 Sao Paulo, Brazil
关键词
D O I
10.1210/me.13.1.156
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Despite advances in characterizing the pathophysiology and genetics of pituitary tumors, molecular mechanisms of their pathogenesis are poorly understood. Recently, we isolated a transforming gene [pituitary tumor-transforming gene (PTTG)] from rat pituitary tumor cells. Here we describe the cloning of human PTTG, which is located on chromosome 5q33 and shares striking sequence homology with its rat counterpart. Northern analysis revealed PTTG expression in normal adult testis, thymus, colon, small intestine, brain, lung, and fetal liver, but most abundant levels of PTTG mRNA were observed in several carcinoma cell lines. Stable transfection of NIH 3T3 cells with human PTTG cDNA caused anchorage-independent transformation in vitro and induced in vivo tumor formation when transfectants were injected into athymic mice. Overexpression of PTTG in transfected NIH 3T3 cells also stimulated expression and secretion of basic fibroblast growth factor, a human pituitary tumor growth-regulating factor. A proline-rich region, which contains two PXXP motifs for the SH3 domain-binding site, was detected in the PTTG protein sequence. When these proline residues were changed by site-directed mutagenesis, PTTG in vitro transforming and in vivo tumor-inducing activity, as well as stimulation of basic fibroblast growth factor, was abrogated. These results indicate that human PTTG, a navel oncogene, may function through SH3-mediated signal transduction pathways and activation of growth factor(s).
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页码:156 / 166
页数:11
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