[The erbB-related protooncogenes encoding growth factor receptors]

Area of Science:

• Molecular Biology
• Oncology
• Genetics

Background:

• The c-erbB-2 gene was identified through cross-hybridization with v-erbB.
• Sequence analysis indicates c-erbB-2 encodes a growth factor receptor homologous to the EGF receptor.

Purpose of the Study:

• To characterize the c-erbB-2 gene product and its function.
• To investigate the potential role of c-erbB-2 in cancer, specifically adenocarcinomas.

Main Methods:

• Nucleotide sequence analysis of cDNA clones.
• Antibody immunoprecipitation and in vitro kinase assays.
• Southern blot analysis of tumor DNA.
• Screening of genomic and cDNA libraries.

Main Results:

• The c-erbB-2 protein is an 185-kDa glycoprotein with protein-tyrosine kinase activity.
• EGF and TGF-alpha do not bind to the c-erbB-2 protein.
• Phosphorylation of c-erbB-2 is stimulated by TPA and EGF, involving protein kinase C and potentially EGF receptor kinase activity.
• The c-erbB-2 gene is frequently amplified in stomach and breast adenocarcinomas.
• Novel yes-related genes (fyn, lyn) and other related genes (c-yes, c-fgr, c-src) were identified.

Conclusions:

• The c-erbB-2 protein functions as a growth factor receptor with distinct binding properties.
• Amplification of the c-erbB-2 gene in adenocarcinomas suggests its involvement in tumorigenesis.
• Identification of related tyrosine kinase genes expands the understanding of this gene family.