Current perspectives on the pathogenesis of clinically non-functioning pituitary tumours

Gittoes, Neil

doi:10.1677/joe.0.1570177

Cited by 22 publications

(14 citation statements)

References 86 publications

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“…Other precocious developmental factors -Pitx factors, Hesx1, PROP-1, have already been observed in normal adult and adenomatous pituitaries (Nakamura et al 1999, Pellegrini-Bouiller et al 1999, Mantovani et al 2006. The preferential expression of Ngn2 in secreting PA appears to be related to tumour phenotype rather than to tumorigenesis itself for a series of reasons: (1) Ngn2 expression is unrelated to tumour volume or aggressiveness; (2) its lower expression in CNS adenomas may reflect the common gonadotroph origin of these tumours (Gittoes 1998) -indeed -the lowest expression was found in gonadotroph adenomas; (3) the highest levels of Ngn2 in CNS were observed in two silent secreting CNS and (4) the higher expression of Ngn2 in Pit-1-dependent PA which received pre-operative pharmacological therapy suggests that the control of mammosomatotroph cell proliferation is associated with Ngn2 expression-accordingly, Ngn2 expression tended to be lower in Pit-1-dependent PA expressing a high Ki-67 index. This point would deserve further investigation.…”

Section: Discussionmentioning

confidence: 96%

Differential expression of neurogenins and NeuroD1 in human pituitary tumours

Fratticci

Grieco

Spilioti

et al. 2007

Journal of Endocrinology

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Basic helix-loop-helix (bHLH) transcription factors are involved in neuroendocrine cell growth and differentiation. Though NeuroD1 is viewed as corticotroph specific, its overexpression in non-corticotroph pituitary adenomas (PAs) may reflect the activation of molecular pathways involving other bHLH factors, like neurogenins. To search for neurogeninNeuroD1 molecular pathways in the human normal and tumoural pituitary. Fifty-one PAs -22 clinically non-secreting (CNS) and 29 secreting respectively -and normal human pituitaries (NP) were studied for NeuroD1 and neurogenins (Ngn1, Ngn2 and Ngn3) gene expression by RT-PCR and quantitative real-time RT-PCR (qRT-PCR). Immunohistochemistry for Ngn2/3 was performed in some cases. NeuroD1, Ngn2, Ngn3 and Ngn1 were observed in up to 84 . 3, 76 . 5, 30 . 4 and 9 . 1% of PA respectively, only NeuroD1 and Ngn2 being frequently overexpressed when compared with NP. Whereas NeuroD1 expression was higher in corticotroph and CNS adenomas (PZ0 . 0001 versus Pit-1-dependent PA), Ngn2 expression was higher in secreting PA, especially in Pit-1-dependent PA (PZ0 . 007 and PZ0 . 0006 versus CNS respectively). Pit-1-dependent PAwhich received pre-operative pharmacological treatment expressed higher Ngn2 levels than untreated cases (PZ0 .

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Section: Discussionmentioning

confidence: 96%

Differential expression of neurogenins and NeuroD1 in human pituitary tumours

Fratticci

Grieco

Spilioti

et al. 2007

Journal of Endocrinology

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“…In nonfunctional tumors, reduced levels of expression of the retinoid X receptor, estrogen receptor, and thyroid hormone receptor have been found and may contribute to abnormal thyroid hormone regulation of a-subunit production in these tumors. However, the significance of these data to pituitary tumorigenesis is unknown (13). The epidermal growth factor receptor (EGFR) is overexpressed in 80% of nonfunctional adenomas and is virtually undetectable in functional adenomas.…”

Section: Introductionmentioning

confidence: 99%

Novel Molecular Signaling and Classification of Human Clinically Nonfunctional Pituitary Adenomas Identified by Gene Expression Profiling and Proteomic Analyses

Moreno

Evans

Zhan³

et al. 2005

Cancer Research

193

182

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Pituitary adenomas comprise 10% of intracranial tumors and occur in about 20% of the population. They cause significant morbidity by compression of regional structures or the inappropriate expression of pituitary hormones. Their molecular pathogenesis is unclear, and the current classification of clinically nonfunctional tumors does not reflect any molecular distinctions between the subtypes. To further elucidate the molecular changes that contribute to the development of these tumors and reclassify them according to the molecular basis, we investigated 11 nonfunctional pituitary adenomas and eight normal pituitary glands, using 33 oligonucleotide GeneChip microarrays. We validated microarray results with the reverse transcription real-time quantitative PCR, using a larger number of nonfunctional adenomas. We also used proteomic analysis to examine protein expression in these nonfunctional adenomas. Microarray analysis identified significant increases in the expression of 115 genes and decreases in 169 genes, whereas proteomic analysis identified 21 up-regulated and 29 down-regulated proteins. We observed changes in expression of SFRP1, TLE2, PITX2, NOTCH3, and DLK1, suggesting that the developmental Wnt and Notch pathways are activated and important for the progression of nonfunctional pituitary adenomas. We further analyzed gene expression profiles of all nonfunctional pituitary subtypes to each other and identified genes that were affected uniquely in each subtype. These results show distinct gene and protein expression patterns in adenomas, provide new insight into the pathogenesis and molecular classification of nonfunctional pituitary adenomas, and suggest that therapeutic targeting of the Notch pathway could be effective for these tumors. (Cancer Res 2005; 65(22): 10214-22)

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“…About 25-30% of pituitary adenomas are non-functioning (1). The definition of non-functioning pituitary adenoma (NFPA) refers to strictly clinical features of these tumors, since immunohistochemistry studies demonstrate that the majority of NFPAs do synthesize and sometimes secrete hormones.…”

Section: Introductionmentioning

confidence: 99%

“…In most cases the produced substances are subunits of glycoprotein hormones (luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyrotropin), mainly the common a-subunit (1), but occasionally also intact glycoprotein hormones have been reported to be produced (2,3). About 17% of NFPAs are pure 'null' adenomas, likely derived from neoplastic transformation of hormonally inactive transitional, undifferentiated or precursor cells, identified in normal pituitaries (1,4).…”

Section: Introductionmentioning

confidence: 99%

Somatostatin and its analog lanreotide inhibit the proliferation of dispersed human non-functioning pituitary adenoma cells in vitro

Florio

Thellung

Arena

et al. 1999

European Journal of Endocrinology

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Objective: Somatostatin is a powerful inhibitor of hormone secretion and cell proliferation. Treatment with somatostatin analogs in humans causes a reduction in size and secretory activity of some endocrine tumors, including somatotropic pituitary adenomas. Less studied are the effects of somatostatin agonists on non-functioning pituitary adenomas (NFPAs). In this study we characterized the effects of somatostatin and its analog lanreotide on the proliferation of NFPAs in vitro and the intracellular mechanisms involved. Design: Twenty-three NFPA post-surgical specimens were analyzed for somatostatin receptor (SSTR) expression and 12 of them were cultured in vitro to study somatostatin's effects on cell proliferation, assessed by means of [ 3 H]thymidine uptake, and the intracellular signaling. Results: One or more SSTR subtypes were expressed in 90% of the adenomas tested. Somatostatin and lanreotide treatment inhibited phorbol myristate acetate (PMA)-induced cell proliferation. Vanadate pretreatment reversed somatostatin and lanreotide inhibition of PMA-induced DNA synthesis suggesting an involvement of tyrosine phosphatase in this effect. In the only adenoma tested, somatostatin directly induced a tyrosine phosphatase activity. Somatostatin and lanreotide caused also a significant inhibition of voltage-sensitive calcium channel activity induced by 40 mmol/l K + depolarization in microfluorimetric analysis. Conclusions: These data show that somatostatin and lanreotide inhibit human NFPA cell proliferation in vitro, and suggest that activation of tyrosine phosphatases and inhibition of the activity of voltage-dependent calcium channels may represent intracellular signals mediating this effect.

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Current perspectives on the pathogenesis of clinically non-functioning pituitary tumours

Cited by 22 publications

References 86 publications

Differential expression of neurogenins and NeuroD1 in human pituitary tumours

Differential expression of neurogenins and NeuroD1 in human pituitary tumours

Novel Molecular Signaling and Classification of Human Clinically Nonfunctional Pituitary Adenomas Identified by Gene Expression Profiling and Proteomic Analyses

Somatostatin and its analog lanreotide inhibit the proliferation of dispersed human non-functioning pituitary adenoma cells in vitro

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