TISSUE AND TUMOR EXPRESSION OF A CELL-SURFACE GLYCOPROTEIN COMPLEX CONTAINING AN INTEGRAL MEMBRANE GLYCOPROTEIN ACTIVATOR OF P185(NEU)

Ascites 13762 rat mammary adenocarcinoma cells contain an abundant het erodimeric cell surface glycoprotein complex. It is composed of a tran smembrane subunit and a sialomucin subunit and is the product of a sin gle gene. The transmembrane subunit has two EGF-like domains and activ ates the proto-oncogene receptor kinase p185(neu). Southern blot compa risons of the ascites tumor and rat liver demonstrated the presence of the gene encoding the complex in normal tissues and showed an amplifi cation of about fivefold in the ascites tumor. Polymerase chain reacti on assays showed the presence of mRNA for the complex in rat brain and lung, but not in liver, pancreas, placenta,intestine, kidney, ovary a nd uterus. Northern blot analyses showed that the 9 kb transcript for the complex is expressed at an approximately 500-fold higher level in the ascites cells than in rat brain. Immunocytochemical studies using antiserum directed against the transmembrane subunit showed its presen ce in bronchial epithelium, brain ependymal and neurons of four day ol d animals and in the endoderm and neuronal cells of embryos. Similar i mmunocytochemical studies showed the presence of the transmembrane sub unit in some human breast tumors. These results suggest that the gene encoding this complex is regulated in a tissue-specific manner, is ove rexpressed in some tumors and may play a role in tumor progesssion.