SAGE analysis highlights the putative role of underexpression of ribosomal proteins in GH-secreting pituitary adenomas

Autor(es):Mostrar menos -

de Lima, Deison Soares ^[1] ; Martins, Clarissa Silva ^[1] ; de Carvalho Paixao, Beatriz Maria ^[1] ; Amaral, Fernando Colbari ^[1] ; Colli, Leandro Machado ^[1] ; Saggioro, Fabiano P. ^[2] ; Neder, Luciano ^[2] ; Machado, Helio Rubens ^[3] ; Dinarte dos Santos, Anemari Ramos ^[4] ; Pinheiro, Daniel G. ^[4] ; Moreira, Ayrton Custodio ^[1] ; Silva, Jr., Wilson Araujo ^[4] ; Castro, Margaret ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Internal Med, Sch Med Ribeirao Preto, BR-14049900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Pathol, Sch Med Ribeirao Preto, BR-14049900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Anat & Surg, Sch Med Ribeirao Preto, BR-14049900 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Genet, Sch Med Ribeirao Preto, BR-14049900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 167, n. 6, p. 759-768, DEC 2012.
• Citações Web of Science: 3

Resumo

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. Conclusion: 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. (AU)

• Processo FAPESP: 07/51004-5 - Expressao genica diferencial em tumores hipofisarios secretores de hormonio de crescimento
• Beneficiário: Deison Soares de Lima
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 07/58365-3 - Fisiopatologia e etiopatogenia molecular de doenças relacionadas aos eixos corticotrófico, somatotrófico e neurohipofisário
• Beneficiário: Margaret de Castro
• Modalidade de apoio: Auxílio à Pesquisa - Temático