Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The differential gene expression of proopiomelanocortin (POMC)-related processing enzymes, transcription factors, and receptors responsible for ACTH secretion between non-pituitary and pituitary ACTH-secreting tumors remains obscure. This study was attempted to determine the gene expression profiles of transcription factors (Tpit, NeuroD1 and IKZF1), proprotein convertase (PC) 1/3 and PC2, and several key receptors linked to ACTH secretion, including corticotrophin releasing hormone receptor (CRHR1), vasopressin receptor 1b (V1bR), somatostatin receptor (SSTR) subtype-2, -5 and dopamine receptor type 2 (D2R) in non-pituitary and pituitary ACTH-secreting tumors. Surgical tissue specimens from carcinoid tumors causing ectopic ACTH syndrome (EAS: n=4) and pituitary tumors causing Cushing's disease (CD: n=13), were subjected to real-time RT-PCR for measurements of each mRNA levels. POMC and CRHR1 mRNA levels in CD were far greater than those in EAS, whereas IKZF1, PC2, SSTR-2 and -5 mRNA levels in EAS were significantly greater than those in CD. NeuroD1, Tpit, PC1/3, V1bR and D2R mRNA levels were comparable between EAS and CD. In conclusion, differential gene expression profiles revealed more abundant mRNA expression in EAS than in CD of 1) IKZF1 with its potential implication of cell differentiation and hormone secretion, 2) PC2 with its possible enhanced processing activity of mature ACTH, and 3) SSTR-2 and -5 with their potential therapeutic application of more selective agonists in EAS patients.
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PMID:Differential gene expression profiles of POMC-related enzymes, transcription factors and receptors between non-pituitary and pituitary ACTH-secreting tumors. 2138 26

Small cell carcinoma (SmCC) and large cell neuroendocrine carcinoma (LENEC) are categorized as neuroendocrine cancers (NECs) of the lung and have extremely poor prognoses. The lack of an effective therapeutic strategy against SmCC and LCNEC is a serious issue. Because the regulation of the cellular phenotype is complicated by the actions of various transcription factors, investigations into the function of neural/neuroendocrine cell-specific transcription factors are important for elucidating the cellular characteristics and histogenesis of SmCC and LCNEC and for establishing innovative therapeutic strategies against them. In this review, the functions of ASCL1, NeuroD1, REST, TTF1, and class III/IV POU, that are specifically and highly expressed in lung NECs, are introduced. These transcription factors transactivate and/or transrepress various genes and are involved in neural progenitor phenotyping, neuroendocrine and stem cell marker expression, and epithelial-to-mesenchymal transition. Based on the evidence that certain carcinoids express ASCL1, NeuroD1, TTF1, and class III/IV POU and that lung NECs can develop from non-NE cells/non-NEC cells, the relationships among lung NECs, carcinoid tumors, and non-NECs are discussed. Finally, a model of the histogenesis of lung NECs in view of similarities in the expression of primitive neural/neuroendocrine cell-specific transcription factors is proposed.
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PMID:Recent advances in histogenesis research of lung neuroendocrine cancers: Evidence obtained from functional analyses of primitive neural/neuroendocrine cell-specific transcription factors. 2570 44