Structure, Expression, and Function of Human Pituitary Tumor-Transforming Gene (PTTG)

• DOI: 10.1210/mend.13.1.0225
• Publication Date: 2014-01-08T17:29:59Z
• Authors: Xun Zhang; Gregory A. Horwitz; Toni R. Prezant; Alberto Valentini; Masahiro Nakashima; Marcello D. Brons...; Shlomo Melmed
• Keywords: 0301 basic medicine; Base Sequence; Carcinogenicity Tests; Molecular Sequence Data; Mice, Nude; 3T3 Cells; Neoplasm Proteins; Rats; Securin; Mice; 03 medical and health sciences; Cell Transformation, Neoplastic; Gene Expression Regulation; Animals; Chromosomes, Human, Pair 5; Humans; Point Mutation; Fibroblast Growth Factor 2; Amino Acid Sequence; Cloning, Molecular

Abstract Despite advances in characterizing the pathophysiology and genetics of pituitary tumors, molecular mechanisms their pathogenesis are poorly understood. Recently, we isolated a transforming gene [pituitary tumor-transforming (PTTG)] from rat tumor cells. Here describe cloning human PTTG, which is located on chromosome 5q33 shares striking sequence homology with its counterpart. Northern analysis revealed PTTG expression normal adult testis, thymus, colon, small intestine, brain, lung, fetal liver, but most abundant levels mRNA were observed several carcinoma cell lines. Stable transfection NIH 3T3 cells cDNA caused anchorage-independent transformation vitro induced vivo formation when transfectants injected into athymic mice. Overexpression transfected also stimulated secretion basic fibroblast growth factor, growth-regulating factor. A proline-rich region, contains two PXXP motifs for SH3 domain-binding site, was detected protein sequence. When these proline residues changed by site-directed mutagenesis, tumor-inducing activity, as well stimulation abrogated. These results indicate that novel oncogene, may function through SH3-mediated signal transduction pathways activation factor(s).