Analysis of proopiomelanocortin gene transcription mechanisms in bronchialtumour cells

The ectopic ACTH syndrome results from the transcription of the proopiomela nocortin (POMC) gene in non pituitary tumors. To determine its mechanisms, we examined in the human bronchial carcinoma cell line DMS-79 transacting f actors binding to the human POMC gene promoter. Three binding sites were id entified in the proximal promoter and proteins were studied by gel-shift as says. One of them is a binding site for Nur77/Nurr1 proteins in corticotrop h cells but is bound in DMS-79 cells by factor(s) distinct from these prote ins. The remaining two binding sites bound yet unidentified proteins and we re both functionally active in DMS-79 cells. We also showed that DMS-79 cel ls lacked a factor required for tissue-restricted POMC gene expression in c orticotroph cells. Altogether, our results indicate that POMC gene expressi on 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 invo lved in the regulation by cAMP and glucocorticoids. (C) 1999 Elsevier Scien ce Ireland Ltd. All rights reserved.