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Cushing's syndrome due to ectopic proopiomelanocortin gene expression by islet cell carcinoma of the pancreas
Author(s) -
Melmed Shlomo,
Yamashita Shunichi,
Kovacs Kalman,
Ong John,
Rosenblatt Sidney,
Braunstein Glenn
Publication year - 1987
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19870215)59:4<772::aid-cncr2820590418>3.0.co;2-h
Subject(s) - proopiomelanocortin , endocrinology , medicine , prohormone , biology , pancreas , pituitary tumors , adrenocorticotropic hormone , gene expression , microbiology and biotechnology , gene , hormone , biochemistry
Abstract Expression of proopiomelanocortin (POMC) was studied in a male patient with Cushing's syndrome and ectopic production of ACTH by a pancreatic carcinoma. Plasma ACTH levels (>200 pg/ml) were elevated, and elevated serum cortisol and urinary free cortisol were partially suppressed to 25% of basal levels by high‐dose dexamethasone. Petrosal and jugular vein sampling did not yield a gradient of ACTH. Immunohistochemical staining of tumor tissue removed at pancreatectomy was positive for ACTH and beta endorphin, and negative for corticotropin‐releasing factor (CRF). Tumor cells cultured in vitro secreted ACTH and beta‐endorphin, which comigrated with their respective radiolabeled standards on gel chromatography. Hydrocortisone suppressed in vitro ACTH secretion and CRF (100 nM) stimulated ACTH by 50% during 72 hours of incubation. Agarose gel electrophoresis of poly‐(A) mRNA extracts of tumor tissue followed by hybridization with 32 P‐cDNA for POMC revealed 2 distinct RNA species. The major RNA species (about 1.0 kb) was smaller than authentic pituitary POMC mRNA (about 1.1 kb); a larger precursor band also was visualized, suggesting either processing or degradation of tumor‐POMC mRNA. Cytoplasmic dot blot hybridization of tumor mRNA with POMC cDNA yielded a positive signal with increasing amounts of RNA blotted. Immunohistochemistry and radioimmunoassay (RIA) of ACTH, in vitro regulation of ACTH secretion, and expression of POMC mRNA species by this tumor document expression of the human POMC gene by an islet carcinoma associated with Cushing's syndrome. Cancer 59:772‐778, 1987.