pG2 gene expression and its regulation in human adrenocortical and medullary tumors

The cDNA clone pG2 was originally isolated from a human pheochromocytoma. T he respective gene was found to be strongly expressed in normal adrenal zon a glomerulosa and medulla, as well as in Conn's adenomas and pheochromocyto mas, To shed more light on the expression and regulation of the pG2 gene, w e investigated its expression in a wide variety of different adrenal neopla sms and cultured adrenal cells. Northern blot analysis was used to determin e the steady state level of pG2 mRNA. Besides normal adrenals, Conn's adeno mas and pheochromocytomas, we found abundant expression of pG2 mRNA in Cush ing's, virilizing and nonfunctional adrenocortical adenomas and carcinomas, as well as in hyperplastic adrenals, The relative levels of pG2 mRNA in va rious adrenocortical tumors were not significantly different from those in normal adrenals and pheochromocytomas. In primary cultures of normal adrena l cells, treatment with adrenocorticotropin induced a 3- to 15-fold increas e in the expression of pG3 mRNA (P < 0.01), and this effect was reproduced by incubation with (Bu)(2)cAMP. In cultured pheochromocytoma cells, treatme nt with (Bu)(2)cAMP and a protein kinase inhibitor, staurosporine, increase d pG2 mRNA accumulation (2- to 4-fold over the control level, P < 0.01, and 3- to 8-fold, P < 0.01, respectively), These results indicate that pG2 is widely expressed in normal and pathological adrenal tissues from both corti cal and medullary origin, which eliminates its usefulness as a specific mar ker for zona glomerulosa or medullary adrenal tumors. Accumulation of pG2 m RNA is regulated by multiple differentiating factors through different path ways in primary cultures of normal adrenal and pheochromocytoma cells.