title: SAGE analysis highlights the putative role of underexpression of ribosomal proteins in GH-secreting pituitary adenomas.
abstract: BACKGROUND
  Although the molecular pathogenesis of pituitary adenomas has been assessed by several different techniques, it still remains partially unclear. Ribosomal proteins (RPs) have been recently related to human tumorigenesis, but they have not yet been evaluated in pituitary tumorigenesis.
  
  
  OBJECTIVE
  The aim of this study was to introduce serial analysis of gene expression (SAGE), a high-throughput method, in pituitary research in order to compare differential gene expression.
  
  
  METHODS
  Two SAGE cDNA libraries were constructed, one using a pool of mRNA obtained from five GH-secreting pituitary tumors and another from three normal pituitaries. Genes differentially expressed between the libraries were further validated by real-time PCR in 22 GH-secreting pituitary tumors and in 15 normal pituitaries.
  
  
  RESULTS
  Computer-generated genomic analysis tools identified 13,722 and 14,993 exclusive genes in normal and adenoma libraries respectively. Both shared 6497 genes, 2188 were underexpressed and 4309 overexpressed in tumoral library. In adenoma library, 33 genes encoding RPs were underexpressed. Among these, RPSA, RPS3, RPS14, and RPS29 were validated by real-time PCR.
  
  
  CONCLUSIONS
  We report the first SAGE library from normal pituitary tissue and GH-secreting pituitary tumor, which provide quantitative assessment of cellular transcriptome. We also validated some downregulated genes encoding RPs. Altogether, the present data suggest that the underexpression of the studied RP genes possibly collaborates directly or indirectly with other genes to modify cell cycle arrest, DNA repair, and apoptosis, leading to an environment that might have a putative role in the tumorigenesis, introducing new perspectives for further studies on molecular genesis of somatotrophinomas.
authors.affiliation: Department of Internal Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Deison Soares
authors.initials: DS
authors.lastname: de Lima
authors.forename: Clarissa Silva
authors.initials: CS
authors.lastname: Martins
authors.forename: Beatriz Maria de Carvalho
authors.initials: BM
authors.lastname: Paixao
authors.forename: Fernando Colbari
authors.initials: FC
authors.lastname: Amaral
authors.forename: Leandro Machado
authors.initials: LM
authors.lastname: Colli
authors.forename: Fabiano P
authors.initials: FP
authors.lastname: Saggioro
authors.forename: Luciano
authors.initials: L
authors.lastname: Neder
authors.forename: Helio Rubens
authors.initials: HR
authors.lastname: Machado
authors.forename: Anemari Ramos Dinarte
authors.initials: AR
authors.lastname: dos Santos
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pinheiro
authors.forename: Ayrton Custodio
authors.initials: AC
authors.lastname: Moreira
authors.forename: Wilson Araújo
authors.initials: WA
authors.lastname: Silva
authors.forename: Margaret
authors.initials: M
authors.lastname: Castro
mesh_terms: D000172:Acromegaly / Q000235:genetics / Q000378:metabolism; D000328:Adult; D002864:Chromogranins; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D015723:Gene Library; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010902:Pituitary Gland / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002864:Chromogranins; D047908:Intracellular Signaling Peptides and Proteins; D012269:Ribosomal Proteins; C103265:aryl hydrocarbon receptor-interacting protein; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs