title: Hmga1 null mouse embryonic fibroblasts display downregulation of spindle assembly checkpoint gene expression associated to nuclear and karyotypic abnormalities.
abstract: The High Mobility Group A1 proteins (HMGA1) are nonhistone chromatinic proteins with a critical role in development and cancer. We have recently reported that HMGA1 proteins are able to increase the expression of spindle assembly checkpoint (SAC) genes, thus impairing SAC function and causing chromosomal instability in cancer cells. Moreover, we found a significant correlation between HMGA1 and SAC genes expression in human colon carcinomas. Here, we report that mouse embryonic fibroblasts null for the Hmga1 gene show downregulation of Bub1, Bub1b, Mad2l1 and Ttk SAC genes, and present several features of chromosomal instability, such as nuclear abnormalities, binucleation, micronuclei and karyotypic alterations. Interestingky, also MEFs carrying only one impaired Hmga1 allele present karyotypic alterations. These results indicate that HMGA1 proteins regulate SAC genes expression and, thereby, genomic stability also in embryonic cells.
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale del CNR and Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II" , Naples , Italy.
authors.forename: Giovanna Maria
authors.initials: GM
authors.lastname: Pierantoni
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale del CNR and Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II" , Naples , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Conte
authors.affiliation: b Istituto di Biologia e Patologie Molecolari del CNR c/o Università "Sapienza" di Roma , Rome , Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Rinaldo
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale del CNR and Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II" , Naples , Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Tornincasa
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale del CNR and Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II" , Naples , Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Gerlini
authors.affiliation: b Istituto di Biologia e Patologie Molecolari del CNR c/o Università "Sapienza" di Roma , Rome , Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Valente
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale del CNR and Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II" , Naples , Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Izzo
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale del CNR and Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II" , Naples , Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000473:pathology; D043171:Chromosomal Instability; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D059565:G2 Phase Cell Cycle Checkpoints; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D025741:HMGA1a Protein / Q000172:deficiency / Q000235:genetics*; D059785:Karyotype; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D048629:Micronuclei, Chromosome-Defective; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C584278:Bub1b protein, mouse; D018797:Cell Cycle Proteins; C000612540:Mad2l1bp protein, mouse; D009687:Nuclear Proteins; D025741:HMGA1a Protein; C441620:Ttk protein, mouse; C584281:Bub1 protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: Chromosome instability; HMGA1; SAC