[ACTH-secreting tumors. Deregulation of the proopiomelanocortin gene and alterations in processing].
ACTH is produced by proteolysis of a polypeptide precursor, proopiomelanocortin (or POMC). Various POMC-derived peptides are cosecreted with ACTH. Analysis of the ACTH--and its "satellite" peptides--molecular forms establishes the POMC "maturation profile" in different tissues. This profile is identical in normal and tumoral pituitaries (Cushing's disease and/or Nelson's syndrome). It is often altered in non-pituitary tumors responsible for the ectopic ACTH syndrome: abnormal peptides may be generated (CLIP h beta MSH5-22) which can be detected in blood. Analysis of POMC gene transcription in pituitary tumors shows no abnormality. In some non-pituitary tumors the activation of upstream promoters up to 369 nucleotides from the normal (pituitary) transcription initiation site can be shown. In normal non-pituitary tissues a third type of transcription is observed generating a short and probably non-functional messenger RNA limited to a portion of the gene non-coding region.
Bertagna
X
X
Centre de Recherche sur les Maladies Endocriniennes, Hôpital Cochin, Paris.
De Keyzer
Y
Y
Kahn
A
A
Girard
F
F
Luton
J P
JP
D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D005786:Gene Expression Regulation; D006729:Hormones, Ectopic / Q000378:metabolism; D006801:Humans; D007158:Immunologic Techniques; D010446:Peptide Fragments / Q000276:immunology; D010673:Pheochromocytoma / Q000235:genetics; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D006729:Hormones, Ectopic; D010446:Peptide Fragments; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone
Les tumeurs ACTH sécrétantes. Dérégulation du gène de la proopiomélanocortine et pathologie de la maturation.