title: PIT1 upregulation by HMGA proteins has a role in pituitary tumorigenesis.
abstract: We have previously demonstrated that HMGA1B and HMGA2 overexpression in mice induces the development of GH and prolactin (PRL) pituitary adenomas mainly by increasing E2F1 transcriptional activity. Interestingly, these adenomas showed very high expression levels of PIT1, a transcriptional factor that regulates the gene expression of Gh, Prl, Ghrhr and Pit1 itself, playing a key role in pituitary gland development and physiology. Therefore, the aim of our study was to identify the role of Pit1 overexpression in pituitary tumour development induced by HMGA1B and HMGA2. First, we demonstrated that HMGA1B and HMGA2 directly interact with both PIT1 and its gene promoter in vivo, and that these proteins positively regulate Pit1 promoter activity, also co-operating with PIT1 itself. Subsequently, we showed, by colony-forming assays on two different pituitary adenoma cell lines, GH3 and αT3, that Pit1 overexpression increases pituitary cell proliferation. Finally, the expression analysis of HMGA1, HMGA2 and PIT1 in human pituitary adenomas of different histological types revealed a direct correlation between PIT1 and HMGA expression levels. Taken together, our data indicate a role of Pit1 upregulation by HMGA proteins in pituitary tumours.
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli Federico II, Naples, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Palmieri
authors.forename: Teresa
authors.initials: T
authors.lastname: Valentino
authors.forename: Ivana
authors.initials: I
authors.lastname: De Martino
authors.forename: Francesco
authors.initials: F
authors.lastname: Esposito
authors.forename: Paolo
authors.initials: P
authors.lastname: Cappabianca
authors.forename: Anne
authors.initials: A
authors.lastname: Wierinckx
authors.forename: Michela
authors.initials: M
authors.lastname: Vitiello
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lombardi
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Trouillas
authors.forename: Giovanna Maria
authors.initials: GM
authors.lastname: Pierantoni
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.forename: Monica
authors.initials: M
authors.lastname: Fedele
mesh_terms: D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism*; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050817:Transcription Factor Pit-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D025743:HMGA2 Protein; C494187:POU1F1 protein, human; D050817:Transcription Factor Pit-1; D025741:HMGA1a Protein; D012313:RNA