Expression of a neu/c-erbB-2-like product in neuroendocrine cells of mammals.

Abstract

The neu/c-erbB-2 oncogene encodes a 185 kDa protein closely homologous to the epidermal growth factor receptor. The protein product (p185) is a glycoprotein with an external domain and an internal domain with tyrosine kinase activity. Amplification and/or overexpression of p185 is related to several human adenocarcinomas. Subsequent studies demonstrated its presence in certain neuroendocrine (NE) neoplasms, including phaeochromocytomas, insulinomas and medullary thyroid carcinomas. However, relatively little is known about its role in normal cell growth regulation and development. Therefore, our objective was to determine whether neu/c-erbB-2 was expressed in normal NE tissues of different mammals, specially in humans, as it was in their neoplasms. We have examined by immunohistochemistry different endocrine glands (thyroid, pancreas, suprarrenal and hypophysis) and the small intestine of human beings, rats and guinea pigs, using two polyclonal antibodies raised against the intracytoplasmic part of the protein, and specific antigen absorption controls. We have found that a neu/c-erbB-2-like product occurs in all normal NE tissues examined: C cells of the thyroid gland, chromaffin cells of the adrenal medulla, pancreatic islets, enteroendocrine cells of the small intestine and, finally, scattered cells of the adenohypophysis, according to a typical granular immunohistochemical pattern. Our results indicate that normal NE cells share a new common antigen in their cytoplasms, a neu/c-erbB-2-like product, with a similar immunostaining pattern to that presented by the neoplasms derived from them.