title: PTTG2 silencing results in induction of epithelial-to-mesenchymal transition and apoptosis.
abstract: Human securin, also known as human pituitary tumor-transforming gene 1 (pttg1), plays a key role in cell-cycle regulation. Two homologous genes, pttg2 and pttg3, have been identified although very little is known about their physiological function. In this study, we aimed at the characterization of these two pttg1 homologs. Real-time PCR analysis using specific probes demonstrated that Pttg2 is expressed at very low levels in various cell lines and tissues whereas Pttg3 was largely undetectable. We focused on the study of Pttg2 and found that, unlike PTTG1, PTTG2 lacks transactivation activity and does not bind to separase, making improbable a role in the control of sister chromatids separation. To further investigate the biological role of pttg2, we used short hairpin RNA inhibition of Pttg2 and found that cells with reduced Pttg2 levels assumed a rounded morphology compatible with a defect in cell adhesion and died by apoptosis in a p53- and p21-dependent manner. Using microarray technology, we generated a gene expression profile of Pttg2-depleted cells versus wild-type cells and found that knockdown of PTTG2 results in concomitant downregulation of E-cadherin and elevated vimentin levels, consistent with EMT induction. The observation of aberrant cellular behaviors in Pttg2-silenced cells reveals functions for pttg2 in cell adhesion and provides insights into a potential role in cell invasion.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER-CSIC), Department of Cell Signaling, Sevilla 41092, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Méndez-Vidal
authors.forename: M del Mar
authors.initials: MM
authors.lastname: Gámez-Del Estal
authors.forename: M A
authors.initials: MA
authors.lastname: Moreno-Mateos
authors.forename: A G
authors.initials: AG
authors.lastname: Espina-Zambrano
authors.forename: B
authors.initials: B
authors.lastname: Torres
authors.forename: J A
authors.initials: JA
authors.lastname: Pintor-Toro
mesh_terms: D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D020869:Gene Expression Profiling; D045325:HCT116 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D064249:Securin; D014404:Tubulin / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D064249:Securin; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; D014746:Vimentin; C578002:pituitary tumor-transforming protein 1, human; C578003:pituitary tumor-transforming protein 2, human