title: Inactivation of PITX2 transcription factor induced apoptosis of gonadotroph tumoral cells.
abstract: Nonfunctioning pituitary adenomas (NFPA; gonadotroph derived), even not inducing hormonal hypersecretion, cause significant morbidity by compression neighboring structures. No effective and specific medical methods are available so far for treating these tumors. The pituitary homeobox 2 (PITX2) gene is a member of the bicoid-like homeobox transcription factor family, which is involved in the Wnt/Dvl/β-catenin pathway. PITX2 is overexpressed in NFPA. PITX2 mutations are known to be responsible for Axenfield Rieger syndrome, a genetic disorder in which pituitary abnormalities have been detected. The R91P mutant identified in Axenfeld Rieger syndrome is a dominant-negative factor, which is able to block the expression of several pituitary genes activated by PITX2. To better understand the role of Pitx2 on gonadotroph tumorigenesis and to explore new approach for inhibiting tumoral growth, the R91P mutant was transferred via a lentiviral vector in tumoral gonadotroph cells of two kinds: the αT3-1 cell line and human adenoma cells. R91P mutant and small interfering RNA directed against Pitx2 both decreased the viability of αT3-1 cells via an apoptotic mechanism involving the activation of executioner caspase. Similar effects of the R91P mutant were observed on human gonadotroph cells in primary culture. Therefore, Pitx2 overexpression may play an antiapoptotic role during NFPA tumorigenesis.
authors.affiliation: Unité Mixte de Recherche 6231, Centre National de la Recherche Scientifique, University of Aix Marseille, 13344 Marseille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Acunzo
authors.forename: Catherine
authors.initials: C
authors.lastname: Roche
authors.forename: Celine
authors.initials: C
authors.lastname: Defilles
authors.forename: Sylvie
authors.initials: S
authors.lastname: Thirion
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Quentien
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: Thomas
authors.initials: T
authors.lastname: Graillon
authors.forename: Henry
authors.initials: H
authors.lastname: Dufour
authors.forename: Thierry
authors.initials: T
authors.lastname: Brue
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pellegrini
authors.forename: Alain
authors.initials: A
authors.lastname: Enjalbert
authors.forename: Anne
authors.initials: A
authors.lastname: Barlier
mesh_terms: D000236:Adenoma / Q000209:etiology* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D052681:Gonadotrophs / Q000473:pathology*; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D010911:Pituitary Neoplasms / Q000209:etiology* / Q000473:pathology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2