title: HMGA2 and p14Arf: major roles in cellular senescence of fibroids and therapeutic implications.
abstract: OBJECTIVE
  To address the influence of genes involved in stem cell self-renewal and senescence on the growth of leiomyoma cells in vitro and to explore possible therapeutic implications of a targeted disruption of the p53-murine double minute 2 (MDM2) interaction.
  
  
  METHODS
  Gene expression studies (qRT-PCR) of fibroid tissue and cells; β-galactosidase stain and qRT-PCR after antagonizing MDM2.
  
  
  RESULTS
  In fibroid cells, expression of HMGA2 decreased with passaging while that of p14(Arf) increased. Expression of these markers significantly positively, and negatively, respectively, influenced proliferation. Administration of nutlin-3, an MDM2 antagonist, induced cellular senescence and increased the expression of BAX. This, along with a significant correlation between p14(Arf) and BAX expression in native fibroids, suggests that p14(Arf) triggers senescence as well as apoptosis.
  
  
  CONCLUSIONS
  p14(Arf) and HMGA2 seem to play a pivotal role in controlling the growth of fibroid cells. Antagonizing MDM2 induces senescence, as well as apoptosis, and may offer a chance to treat fibroids.
authors.affiliation: Center of Human Genetics, University of Bremen, Leobener Strasse ZHG, 28359 Bremen, Germany.
authors.forename: Dominique Nadine
authors.initials: DN
authors.lastname: Markowski
authors.forename: Burkhard Maria
authors.initials: BM
authors.lastname: Helmke
authors.forename: Gazanfer
authors.initials: G
authors.lastname: Belge
authors.forename: Rolf
authors.initials: R
authors.lastname: Nimzyk
authors.forename: Sabine
authors.initials: S
authors.lastname: Bartnitzke
authors.forename: Ulrich
authors.initials: U
authors.lastname: Deichert
authors.forename: Jörn
authors.initials: J
authors.lastname: Bullerdiek
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D025743:HMGA2 Protein / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D010879:Piperazines / Q000494:pharmacology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D025743:HMGA2 Protein; D007093:Imidazoles; D010879:Piperazines; D034741:RNA, Small Interfering; D025803:Tumor Suppressor Protein p14ARF; C482205:nutlin 3; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D001616:beta-Galactosidase