title: Involvement of FKHR (FOXO1) transcription factor in human uterus leiomyoma growth.
abstract: OBJECTIVE
  To study the expression of FOXO1 and pSer256-FOXO1 parallel to Akt and pSer473-Akt in leiomyoma compared with adjacent myometrium from human uteri.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  University departments.
  
  
  METHODS
  Thirty-eight cyclic and 20 menopausal women who underwent hysterectomy for benign indications.
  
  
  METHODS
  None.
  
  
  METHODS
  Western blot analyses were used for evaluation in leiomyoma and adjacent myometrium of Akt and pSer473-Akt, 14-3-3 gamma proteins and expression and subcellular distribution of FOXO1 and pSer256-FOXO1 during the menstrual cycle and at menopause.
  
  
  RESULTS
  The present study demonstrates the expression of FOXO1 and pSer256-FOXO1 at the tissue level in the human uterus leiomyoma and adjacent myometrium. The level of phosphorylated FOXO1 in leiomyoma was higher than in matched myometrium. The pSer256-FOXO1 in leiomyoma during menstrual phases was located mostly in the nuclear fraction comparison to that of the myometrium. The reason for this difference is presumably the simultaneously detected lower level of 14-3-3 protein.
  
  
  CONCLUSIONS
  Abundant level of the phosphorylated FOXO1, its impaired nucleocytoplasmic shuttling, and the lowered expression of 14-3-3 protein in leiomyoma induces a shift in the cellular machinery toward a prosurvival execution program and thus presents a potential therapeutic target for treatment of leiomyoma.
authors.affiliation: Department of Obstetrics and Gynecology, Pécs University Medical School, Pécs, Hungary. Electronic address: kalman.kovacs@aok.pte.hu.
authors.forename: Kálmán A
authors.initials: KA
authors.lastname: Kovács
authors.affiliation: Institute of Physiology, Pécs University Medical School, Pécs, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Lengyel
authors.affiliation: Department of Obstetrics and Gynecology, Pécs University Medical School, Pécs, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Wilhelm
authors.affiliation: Institute of Physiology, Pécs University Medical School, Pécs, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Vértes
authors.affiliation: Department of Biochemistry, Pécs University Medical School, Pécs, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Sumegi
authors.affiliation: Institute of Physiology, Pécs University Medical School, Pécs, Hungary.
authors.forename: Marietta
authors.initials: M
authors.lastname: Vértes
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009215:Myometrium / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D021381:Protein Transport; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D048948:14-3-3 Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D011494:Protein Kinases