Methods of characterizing ligands for the erbB-3 receptor, methods of influencing erbB-3 activities and methods of diagnosing erbB-3-related neoplasm

US5916755A · kind A · utility

Assignee

• The United States of America, as represented by the Department of Health and Human Services · US

Inventors

• Matthias H. Kraus · Bethesda, US
• Stuart A. Aaronson · Great Falls, US

Key dates

• Filing date: Jun 7, 1995
• Grant date: Jun 29, 1999
• Expiry date: Jun 7, 2015

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2500/04
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A DNA fragment distinct from the epidermal growth factor receptor (EGFR) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGFR and erbB-2, plays a role in some human malignancies. Using erbB-3 specific antibodies (polyclonal or monoclonal), the erbB-3 protein was identified as a 180 kDa glycoprotein, gp180.sup.erbB-3. The intrinsic catalytic function of gp180.sup.erbB-3 was uncovered by its ability to autophosphorylate in vitro. These findings, combined with the detection of constitutive tyrosine phosphorylation of gp180.sup.erbB-3 in 4 out of 12 human mammary tumor cell lines, implicate the activated erbB-3 product in the pathogenesis of some human malignancies. Thus,…