title: The WNT/β-catenin signaling pathway and expression of survival promoting genes in luteinized granulosa cells: endometriosis as a paradigm for a dysregulated apoptosis pathway.
abstract: OBJECTIVE
  To analyze the WNT/β-catenin signaling pathway in luteinized granulosa cells from women with and without endometriosis in relation to cellular apoptosis.
  
  
  METHODS
  Basic.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Patients with a laparoscopic diagnosis of endometriosis (n = 30) and women undergoing intracytoplasmic sperm injection for male infertility (control group n = 39).
  
  
  METHODS
  Isolation of luteinized granulosa cells.
  
  
  METHODS
  Gene expression analysis of components of the WNT/β-catenin pathway, protein expression levels of β-catenin, and cell cycle studies in luteinized granulosa cells.
  
  
  RESULTS
  Compared with luteinized granulosa cells from control women, cells derived from endometriosis patients had significantly higher transcript levels of the β-catenin-independent molecules WNT4 and WNT5a and lower levels of the β-catenin-dependent molecule WNT1. A decrease of total β-catenin as well as of its dephosphorylated active form, together with an aberrant gene expression of the downstream targets survivin and BMP4, was detected in cells from affected women. Flow cytometry analysis confirmed an enhanced apoptosis of luteinized granulosa cells from patients with endometriosis.
  
  
  CONCLUSIONS
  The concomitant dysregulation of specific members of the WNT pathway and of its pivot molecule β-catenin in granulosa cells characterized by an increased apoptosis suggests that the WNT/β-catenin signaling pathway might be involved in leading to granulosa cell atresia.
authors.affiliation: Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sanchez
authors.affiliation: Obstetrics and Gynecology Unit, San Raffaele Scientific Institute, Milan, Italy. Electronic address: vigano.paola@hsr.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Viganò
authors.affiliation: Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Quattrone
authors.affiliation: Obstetrics and Gynecology Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Pagliardini
authors.affiliation: Obstetrics and Gynecology Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Papaleo
authors.affiliation: Obstetrics and Gynecology Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Candiani
authors.affiliation: Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Panina-Bordignon
mesh_terms: D000328:Adult; D017209:Apoptosis; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002470:Cell Survival; D002478:Cells, Cultured; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008184:Luteal Cells / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077022:Survivin; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism; D060528:Wnt4 Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; C495270:CTNNB1 protein, human; D051034:Inhibitor of Apoptosis Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000077022:Survivin; C495247:WNT1 protein, human; C555581:WNT4 protein, human; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; D060528:Wnt4 Protein; D051176:beta Catenin
keywords: WNT signalling; endometriosis; luteinized granulosa cells; β-catenin