IMMUNOHISTOCHEMICAL EVIDENCE FOR PROTEIN-KINASE-C IN PRIMARY HUMAN ADRENAL-TUMORS

We investigated the specific expression of protein kinase C (PKC) in primary human adrenal tumors resected surgically, using type-specific monoclonal antibodies MC-1a, -2a and -3a. Included were adrenocortical adenomas (Cushing's syndrome, Conn's syndrome and clinical nonfunctioning), pheochromocytoma and neuroblastoma. Immunoblotting experiments revealed that the adrenal cortex, medulla, adrenocortical adenomas and pheochromocytoma contained type III isozyme as the major subtype, whereas the neuroblastoma expressed both types II and III isozymes. PKC specific antibodies recognized two bands with a molecular mass of 79 and 81 kDa. Immunoreactivity was mainly present in the cytosolic fraction of the adrenal cortex, medulla and adrenocortical adenomas. The translocation of PKC from cytosol to particulate membrane fractions was observed in cases of pheochromocytoma and neuroblastoma. Microscopically, strong immunostaining was present in the zona fasciculata to reticularis of the adrenal cortex, while the zona glomerulosa and medulla demonstrated minimal staining. The intermediate-type and compact-type cells of adrenocortical adenomas gave a strong positive reaction. The MC-2a positive cells of neuroblastoma were limited to the perivascular area. Immunoblotting and electron microscopic observations of the adrenocortical and adenoma cells showed immunoreactive products on the endoplasmic reticulum, mitochondria and plasma membrane, with a different intensity. In addition to the hypothesis that PKC may play an important role in the regulation of steroidogenesis and catecholamine secretion, oar results indicate that the localization of PKC differs in tumors derived from adrenocortical and medullary cells. The possibility that the expression of type II isozyme in neuroblastoma may be associated with neural differentiation would have to be considered.