Molecular and Trophic Mechanisms of Tumorigenesis

Levy, Andrew

doi:10.1016/j.ecl.2007.10.009

Cited by 24 publications

(23 citation statements)

References 115 publications

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“…The involvement of different cyclin D1 alleles, p16 amplification, and methylation are still obscure. Classic proto-oncogenes, such as NRAS, MYCL1, MYCN, HRAS (HRAS1), BCL1 (CCND1), FGF4, Sea, KRAS2 (KRAS), C-erbB-2, and FOS, and tumor suppressors such as retinoblastoma gene (RB1) and P53 do not appear to have a significant role in pituitary adenoma pathogenesis (1,2). Activating mutations, promoter insertions, deletions, or point mutations of PTTG (PTTG1) as well as clear correlation between PTTG expression and mitotic index in human pituitary tumors have not been described.…”

Section: Introductionmentioning

confidence: 99%

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

Lima

Martins

Paixao

et al. 2012

European Journal of Endocrinology

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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 highthroughput 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.

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Section: Introductionmentioning

confidence: 99%

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

Lima

Martins

Paixao

et al. 2012

European Journal of Endocrinology

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“…They result from abnormal lactotroph cell proliferation and usually display only very slow growth, but the pathogenesis of prolactinoma formation and progression has remained elusive. Classical oncogenic mechanisms seem unlikely to be involved in most cases, and none of the common genetic mutations causing cancer has so far been found to operate in prolactinomas (Levy, 2008). A number of proteins have been implicated in pituitary adenoma development; pituitary tumor transforming gene (PTTG) (Kim et al, 2007), basic fibroblast growth factor (bFGF) (Zhang et al, 1999), vascular endothelial growth factor (VEGF) (McCabe et al, 2002), bone morphogenetic protein 4 (BMP4) (Labeur et al, 2010), pituitary tumor apoptosis gene (PTAG) (Bahar et al, 2004) and histone deacetylase 2 (HDAC2) (Bilodeau et al, 2006), among several others, have been demonstrated to play a role in pituitary tumorigenesis but the origins of many tumors are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Wnt signaling in estrogen-induced lactotroph proliferation

Giles

Friedrichsen

et al. 2011

Journal of Cell Science

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SummaryProlactinomas are the most common type of functioning pituitary adenoma in humans, but the control of lactotroph proliferation remains unclear. Here, using microarray analysis, we show that estrogen treatment increased expression of Wnt4 mRNA in adult Fischer rat pituitary tissue. Dual immunofluorescence analysis revealed that Wnt4 expression was not confined to lactotrophs, but that it was expressed in all anterior pituitary cell types. Estradiol induced proliferation in the somatolactotroph GH3 cell line, in parallel with Wnt4 mRNA and protein induction. A reporter gene assay for TCF-and LEF-dependent transcription revealed that there was no activation of the canonical Wnt pathway in GH3 cells upon stimulation with Wnt-conditioned culture medium or coexpression of constitutively active mutant -catenin. Expression of -catenin in both GH3 cells and normal rat anterior pituitary cells was restricted to the cell membrane and was unaltered by treatment with estradiol, with no nuclear -catenin being detected under any of the conditions tested. We show for the first time that Wnt4 affects non-canonical signaling in the pituitary by inhibiting Ca 2+ oscillations in GH3 cells, although the downstream effects are as yet unknown. In summary, Wnt4 is expressed in the adult pituitary gland, and its expression is increased by estrogen exposure, suggesting that its involvement in adult tissue plasticity is likely to involve -cateninindependent signaling pathways.

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“…Os tumores hipofisários podem ser classificados de acordo com sua secreção hormonal em prolactinomas, que representam 50% dos casos; adenomas clinicamente não funcionantes (ACNF) que perfazem 30% dos casos; somatotropinomas, de 15% a 20%; corticotropinomas, de 5% a 10%, sendo mais raros os gonadotropinomas e tireotropinomas (19) . A Figura 3 ilustra a frequência dos tipos de tumores de hipófise, classificados de acordo com a secreção hormonal.…”

Section: Tumores Hipofisáriosunclassified

“…ACNF: adenoma clinicamente não funcionante Figura 3 -Frequência dos tumores de hipófise, classificados de acordo com secreção hormonal (19) Adicionalmente, os tumores hipofisários podem ser classificados de acordo com as dimensões do maior diâmetro em microadenomas (menores que 1 cm), macroadenomas (maiores ou iguais a 1 cm) ou ainda, tumores gigantes, cujo o maior diâmetro mede mais de 4 cm (20) .…”

Section: Tumores Hipofisáriosunclassified

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Análise da expressão da filamina A nos tumores hipofisários e suas implicações clínicas e terapêuticas

Sickler¹

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Dedico esta tese:Aos meus pais, Marilena e Luciano, pelo apoio incondicional, ajuda e exemplo de boas pessoas.Aos meus filhos, Lucas e Rafael, por deixarem a vida doce, e repleta de alegrias em todos os seus momentos.À minha irmã Bruna, por ser sempre sincera e amiga. E principalmente ao Gabriel, pelo amor presente em cada dia que antecedeu a realização e finalização desse estudo; sem você, eu não conseguiria...

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Molecular and Trophic Mechanisms of Tumorigenesis

Cited by 24 publications

References 115 publications

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

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

Wnt signaling in estrogen-induced lactotroph proliferation

Análise da expressão da filamina A nos tumores hipofisários e suas implicações clínicas e terapêuticas

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