title: Human pituitary tumours express the bHLH transcription factors NeuroD1 and ASH1.
abstract: Among the transcription factors involved in pituitary ontogenesis and physiology, basic helix-loop-helix (bHLH) have been poorly studied. Members of bHLH family include NeuroD1 and ASH1, both involved in neuroendocrine differentiation. We evaluated their mRNA expression patterns, by semi-quantitative RT-PCR analysis (sq-RT-PCR) and/or Northern blot, in a series of 33 pituitary adenomas (PA), anterior pituitaries, and pituitary cell lines. Immunohistochemistry for NeuroD1 was also performed in 25 PA. Low levels of NeuroD1 were observed in normal pituitaries and in the somatomammotroph cell lines GH3/GH4C1, contrasting with high levels in corticotroph AtT20 cells. NeuroD1 mRNA was widely expressed in PA (82%), with measurable levels found especially in those derived from Pit-1 independent lineages, i.e. corticotroph (5/5) and clinically non-secreting (CNS) adenomas (9/11). According to sq-RT-PCR analysis, overexpression of NeuroD1 compared to normal pituitaries was frequent. Variable nuclear NeuroD1 immunopositivity was also present in about 70% of studied cases. ASH1 mRNA was widely detected in normal pituitaries, in all tumour cell lines and in most PA (84%), with measurable levels in corticotroph (5/5) and CNS (9/11) adenomas, and in a significant subset of PA derived from Pit-1 dependent lineages (9/16). We conclude that: a) NeuroD1 is differentially expressed in PA and its possible ontogenetic and/or pathogenetic implications in non-corticotroph PA are discussed; b) ASH1 is a neuroendocrine marker whose expression is largely conserved in normal and neoplastic pituitary cells.
authors.affiliation: Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ferretti
authors.forename: D
authors.initials: D
authors.lastname: Di Stefano
authors.forename: F
authors.initials: F
authors.lastname: Zazzeroni
authors.forename: R
authors.initials: R
authors.lastname: Gallo
authors.forename: A
authors.initials: A
authors.lastname: Fratticci
authors.forename: R
authors.initials: R
authors.lastname: Carfagnini
authors.forename: S
authors.initials: S
authors.lastname: Angiulli
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: G
authors.initials: G
authors.lastname: Minniti
authors.forename: G
authors.initials: G
authors.lastname: Tamburrano
authors.forename: E
authors.initials: E
authors.lastname: Alesse
authors.forename: G
authors.initials: G
authors.lastname: Cantore
authors.forename: A
authors.initials: A
authors.lastname: Gulino
authors.forename: M L
authors.initials: ML
authors.lastname: Jaffrain-Rea
mesh_terms: D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins; D015152:Blotting, Northern; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018257:Helix-Loop-Helix Motifs; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D015175:Prolactinoma / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D011495:Histone-Lysine N-Methyltransferase; D011333:Pro-Opiomelanocortin; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D015534:Trans-Activators; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C093970:NEUROD1 protein, human; C494187:POU1F1 protein, human; C490911:ASH1L protein, human