title: All-trans-retinoic acid mediates changes in PI3K and retinoic acid signaling proteins of leiomyomas.
abstract: OBJECTIVE
  To detect changes induced by all-trans-retinoic acid (ATRA) on the expression and activation of target proteins of the retinoic acid (RA) and PI3K/Akt pathways involved in leiomyoma growth.
  
  
  METHODS
  A study on human tissue cultures.
  
  
  METHODS
  Hadassah University Hospital.
  
  
  METHODS
  Premenopausal women with uterine leiomyomas.
  
  
  METHODS
  Paired cultures of normal myometrium and leiomyomas, from women undergoing hysterectomy, were obtained.
  
  
  METHODS
  The effect of ATRA was examined on the expression and phosphorylation of relevant RA, PI3K/Akt, and Bcl2 proteins (immunochemical analysis), cell proliferation, cell cycle distribution, and apoptosis.
  
  
  RESULTS
  Applying our cell culture model, we demonstrated that ATRA induced changes in the expression and activation of the RA and PI3K/Akt pathway proteins in leiomyoma cells, with significant increases of alcohol dehydrogenase 1 and cyclin D2 protein levels. In part of the leiomyoma cells, ATRA induced a relative increase of Bax (proapoptotic) as well as a relative decrease of phosphorylated glycogen synthase kinase 3β (proapoptotic).
  
  
  CONCLUSIONS
  Our results highlight the involvement of ATRA in the RA and PI3K/Akt pathways, whose specific signaling products may influence the outcome of leiomyoma growth by regulating cell proliferation, apoptosis, and survival. These results might be useful for the on-going research into alternative methods for treating and preventing this disorder.
authors.affiliation: Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Ein-Kerem, Jerusalem, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Ben-Sasson
authors.forename: Assaf
authors.initials: A
authors.lastname: Ben-Meir
authors.forename: Asher
authors.initials: A
authors.lastname: Shushan
authors.forename: Laila
authors.initials: L
authors.lastname: Karra
authors.forename: Nathan
authors.initials: N
authors.lastname: Rojansky
authors.forename: Benjamin Y
authors.initials: BY
authors.lastname: Klein
authors.forename: Rubina
authors.initials: R
authors.lastname: Levitzki
authors.forename: Hannah
authors.initials: H
authors.lastname: Ben-Bassat
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism* / Q000473:pathology; D016555:Matched-Pair Analysis; D008875:Middle Aged; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology*; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D019869:Phosphatidylinositol 3-Kinases