Analysis of proopiomelanocortin gene transcription mechanisms in bronchial tumour cells.
The ectopic ACTH syndrome results from the transcription of the proopiomelanocortin (POMC) gene in non pituitary tumors. To determine its mechanisms, we examined in the human bronchial carcinoma cell line DMS-79 transacting factors binding to the human POMC gene promoter. Three binding sites were identified in the proximal promoter and proteins were studied by gel-shift assays. One of them is a binding site for Nur77/Nurr1 proteins in corticotroph cells but is bound in DMS-79 cells by factor(s) distinct from these proteins. The remaining two binding sites bound yet unidentified proteins and were both functionally active in DMS-79 cells. We also showed that DMS-79 cells lacked a factor required for tissue-restricted POMC gene expression in corticotroph cells. Altogether, our results indicate that POMC gene expression in DMS-79 cells is achieved without several of the corticotroph factors and provide a preliminary characterization of some factors involved in this process. They also reveal that DMS-79 cells are deficient in proteins involved in the regulation by cAMP and glucocorticoids.
Picon
A
A
CNRS UPR 1524, Université René Descartes, Institut Cochin de Génétique Moléculaire, CHU Cochin-Port Royal, Paris, France.
Bertagna
X
X
de Keyzer
Y
Y
D000182:ACTH Syndrome, Ectopic / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D001984:Bronchial Neoplasms / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000276:immunology / Q000378:metabolism; D018983:DNA Footprinting; D015342:DNA Probes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D009928:Organ Specificity; D010902:Pituitary Gland / Q000166:cytology; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020218:Response Elements / Q000235:genetics*; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology
D017362:Cyclic AMP Response Element-Binding Protein; D015342:DNA Probes; D004268:DNA-Binding Proteins; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D015534:Trans-Activators; D014157:Transcription Factors; D011333:Pro-Opiomelanocortin