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

Proopiomelanocortin (POMC) gene expression is not restricted to the pituitary corticotroph cell, but also takes place in many normal and tumoral nonpituitary tissues. In contrast, the ectopic ACTH syndrome is a rare event. Because it is most often associated with lung tumors, we specifically studied this tissue, analyzing the different forms of POMC RNAs in normal specimens as well as in various types of tumors. The endocrine nature of the tumors was assessed by both histological examination and measurements of secretogranin-I fragments in the tissue extracts. POMC RNA was first detected by Northern blot analysis; its absolute amounts and its various molecular forms were more precisely quantified and discriminated by S1 mapping studies using a single stranded DNA probe located at the 5' end of exon 3. In five bronchial carcinoid tumors associated with the ectopic ACTH syndrome, a highly predominant, if not single, POMC RNA identical to the 1200-nucleotide (nt) pituitary message was present, the high amounts of which were correlated with those of POMC peptides in the same tissues. In five bronchial carcinoid tumors not associated with the ectopic ACTH syndrome, the same message was detected (four of five), with a second, often predominant, short RNA of about 800 nt (five of five), and the overall amounts of POMC RNAs were low. Similar patterns of POMC RNAs were observed in squamous cell tumors, adenocarcinomas, and normal lung, where the short 800-nt RNA tended to be predominant. These results show that POMC gene expression can be demonstrated in normal lung tissue and in all types of lung tumors. The ectopic ACTH syndrome only occurs with tumors capable of generating high amounts of the pituitary-like message, a phenomenon that seems to be restricted to an occasional tumor with features of neuroendocrine differentiation.
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PMID:Proopiomelanocortin gene expression in normal and tumoral human lung. 185 67

Proopiomelanocortin (POMC) is the common precursor of a variety of important endocrine peptides including ACTH. Transcription of the POMC gene is positively regulated by CRH through cAMP-responsive regions and is under negative feedback control by glucocorticoids which exert their inhibitory effect trough negative glucocorticoid responsive elements (nGRE). In vitro studies using the rat POMC promoter suggested that binding of the glucocorticoid receptor complex to a -63 bp binding site is correlated with repression of POMC gene transcription, and that specific mutations in this region abolish this effect. Impaired negative feedback regulation, though to a different degree, is a common feature of both corticotroph tumors (Cushing's disease) and extrapituitary ACTH producing tumors. We have analyzed the upstream promoter region of POMC gene from eleven patients with Cushing's disease, four of which had Nelson's syndrome, and from one patient with an ectopic ACTH syndrome secondary to a lung carcinoid for any possible mutations in the nGRE and/or cAMP-responsive sequences. DNA was purified from tumor tissue and was used as template for polymerase chain reaction (PCR). A segment between -371 and -19 bp of the POMC transcription start site was amplified and cloned into a plasmid vector. Sequencing was performed using the dideoxy chain termination procedure. Analysis of the 5'-flanking region revealed no defect in all tumors investigated. We conclude from our results that the defective glucocorticoid repression of POMC peptides production may be more likely due to aberrancies in other components of the complex transcriptional regulatory mechanism.
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PMID:Structure of the POMC promoter region in pituitary and extrapituitary ACTH producing tumors. 838 73