title: Overexpression of the truncated form of High Mobility Group A proteins (HMGA2) in human myometrial cells induces leiomyoma-like tissue formation.
abstract: The pathogenesis of uterine leiomyomas, the most common benign tumor in women, is still unknown. This lack of basic knowledge limits the development of novel non-invasive therapies. Our group has previously demonstrated that leiomyoma side population (SP) cells are present in tumor lesions and act like putative tumor-initiating stem cells in human leiomyoma. Moreover, accumulated evidence demonstrates that these benign tumors of mesenchymal origin are characterized by rearrangements of the High Mobility Group A proteins (HMGA). In this work, we tested the hypothesis that leiomyoma development may be due to overexpression of HMGA2 (encoding high mobility group AT-hook2) in myometrial stem cells using in vitro and in vivo approaches. Our work demonstrates that the truncated/short form of HMGA2 induces myometrial cell transformation toward putative tumor-initiating leiomyoma cells and opens up new possibilities to understand the origin of leiomyomas and the development of new therapeutic approaches.
authors.affiliation: Fundación IVI, Instituto Universitario IVI, Department of Obstetrics & Gynecology, School of Medicine, University of Valencia, INCLIVA, Valencia, Spain.
authors.forename: Aymara
authors.initials: A
authors.lastname: Mas
authors.affiliation: Fundación IVI, Instituto Universitario IVI, Department of Obstetrics & Gynecology, School of Medicine, University of Valencia, INCLIVA, Valencia, Spain irene.cervello@ivi.es.
authors.forename: Irene
authors.initials: I
authors.lastname: Cervelló
authors.affiliation: Fundación Instituto Leloir IBBA-CONICET, Buenos Aires, Argentina.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández-Álvarez
authors.affiliation: Fundación IVI, Instituto Universitario IVI, Department of Obstetrics & Gynecology, School of Medicine, University of Valencia, INCLIVA, Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Faus
authors.affiliation: Central Service for Experimental Research, University of Valencia, INCLIVA, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Díaz
authors.affiliation: Department of Pathology, Hospital Clínico Universitario of Valencia, Valencia, Spain.
authors.forename: Octavio
authors.initials: O
authors.lastname: Burgués
authors.affiliation: Biomedical Institute of Valencia (IBV-CSIC), Valencia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Casado
authors.affiliation: Fundación IVI, Instituto Universitario IVI, Department of Obstetrics & Gynecology, School of Medicine, University of Valencia, INCLIVA, Valencia, Spain Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007438:Introns; D007889:Leiomyoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D009215:Myometrium / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014183:Transplantation, Heterologous; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D025743:HMGA2 Protein; D020033:Protein Isoforms
keywords: High Mobility Group A proteins; human myometrium; side population; somatic stem cells; uterine leiomyomas