Expression of the c-erbB-2 gene encoding a growth factor receptor

Area of Science:

• Molecular Biology
• Genetics
• Oncology

Background:

• The c-erbB-2 gene is a proto-oncogene related to the v-erbB oncogene.
• It encodes a protein similar to the epidermal growth factor (EGF) receptor but with distinct properties.
• This gene's location and potential role in cancer require further investigation.

Purpose of the Study:

• To characterize the c-erbB-2 gene, its protein product, and its potential role in human tumors.
• To determine the chromosomal location of the c-erbB-2 gene.
• To investigate the transcriptional regulation of the c-erbB-2 gene in comparison to the EGF receptor gene.

Main Methods:

• In situ hybridization to determine gene location.
• Analysis of mRNA and protein synthesis.
• Tyrosine kinase activity assays.
• Southern blot hybridization for gene amplification analysis.
• Promoter sequence analysis.

Main Results:

• The c-erbB-2 gene is located on human chromosome 17 at q21.
• It encodes a 185 kd glycoprotein with tyrosine kinase activity.
• Gene amplification of c-erbB-2 was observed specifically in adenocarcinomas.
• The c-erbB-2 protein is phosphorylated in response to EGF receptor activation.
• The c-erbB-2 promoter contains TATA, CAAT, and GC boxes, unlike the EGF receptor promoter which only has GC boxes.

Conclusions:

• The c-erbB-2 gene is amplified in adenocarcinomas, suggesting its involvement in tumorigenesis.
• The c-erbB-2 protein is a functional tyrosine kinase and a potential substrate for the EGF receptor.
• Distinct promoter elements indicate different transcriptional control mechanisms for c-erbB-2 and the EGF receptor genes.