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The Gene Expression Profies Of Pituitary Adenomas Studied By CDNA Microarray

Posted on:2006-03-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:J HuFull Text:PDF
GTID:1104360155460507Subject:Endocrine
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Part IThe Gene Expression Profies of Pituitary Adenomas Studied by cDNAMicroarrayObjective To screen differentially expressed gene profiling in pituitary adenomas, compare with that in normal pituitary, and to discuss the possible role of candidate genes in the pathogenesis of pituitary adenoma. Methods The differentially expressed genes in pituitary adenomas were studied by complementary DNA microarrays, and confirmed by RT-PCR and realtime-PCR. Results In comparison with that in normal pituitary, the genes involved in signal transduction pathway, growth and differentiation were mainly differentially expressed. PP4R2, GHRHR and clusterin were significantly highly expressed in PRL, somatotroph and nonfunctioning adenomas respectively, which was also proved by RT-PCR and realtime-PCR. Conclusions PP4R2, GHRHR and clusterin may play a pivotal role in the development of PRL, somatotroph and nonfunctioning adenomas respectively.Part IIGene expression profiling in human null cell pituitary adenoma tissueIt is estimated that up to one in five individuals develops pituitary gland tumors, despite the common occurrence of these tumors, the pathogenetic mechanisms underlying their development mainly remain unknown. We studied the gene expression in null cell adenomas compared with normal pituitary by Expressed Sequence Tags(EST) sequencing and cDNA microarray on large scale. Both approaches of EST sequencing and microarray analysis showed that 9 genes were differentially expressed in human null cell pituitary adenoma tissues, among which 7 genes were overexpressed and 2 genes were underpressed. Five of the genes with potential oncogenic significance were confirmed by RT-realtime quantitative PCR. Synaptotagmin (SYT) is integral membrane proteins of synaptic vesicles considered to serve as Ca2+ sensors in the process of vesicular trafficking and exocytosis. Calcium binding to participates in triggering neurotransmitter release at the synapse. In view of our finding that SYT was overexpressed in null cell adenomas, these tumors might be capable of secreting some unknown hormones or peptides. ATP5B and MDH1 were involved in the energy metabolism, whose overexpression in null cell adenomas provided us with a new perspective of exploring the oncogenesis of these tumors. All of these data may contribute to the understanding of null cell adenoma formation and development.
Keywords/Search Tags:cDNA Microarray, gene expression profiling, pituitary adnoma, protein phosphatase 4(PP4), growth hormone releasing hormone receptor(GHRHR), Clusterin, Expressed Sequence Tags(EST), cDNA Microarray, pituitary null cell adnoma, Synaptotagmin
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