Structure, Expression, and Function of Human Pituitary Tumor-Transforming Gene (PTTG)
| Autor: | Gregory A. Horwitz, Shlomo Melmed, Marcello D. Bronstein, Toni R. Prezant, Masahiro Nakashima, Xun Zhang, Alberto Valentini |
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| Rok vydání: | 1999 |
| Předmět: |
Pituitary gland
Carcinogenicity Tests Molecular Sequence Data Basic fibroblast growth factor Mice Nude Biology Pituitary neoplasm 3T3 cells Mice chemistry.chemical_compound Endocrinology medicine Animals Humans Point Mutation Amino Acid Sequence Cloning Molecular Molecular Biology Messenger RNA Base Sequence Pituitary tumors 3T3 Cells General Medicine Transfection medicine.disease Molecular biology Neoplasm Proteins Rats Securin Cell Transformation Neoplastic medicine.anatomical_structure Gene Expression Regulation chemistry Cell culture Cancer research Chromosomes Human Pair 5 Fibroblast Growth Factor 2 |
| Zdroj: | Molecular Endocrinology. 13:156-166 |
| ISSN: | 1944-9917 0888-8809 |
| DOI: | 10.1210/mend.13.1.0225 |
| Popis: | 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 novel oncogene, may function through SH3-mediated signal transduction pathways and activation of growth factor(s). |
| Databáze: | OpenAIRE |
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