The ERBB2 gene, which encodes the ErbB-2 protein, is located on the long arm of human chromosome 17 (17q12) . The protein itself is composed of an extracellular ligand-binding domain, a transmembrane domain, and an intracellular domain that interacts with various signaling molecules . Unlike other members of the ErbB family, ErbB-2 does not have a ligand-binding domain of its own and cannot bind growth factors directly . Instead, it forms heterodimers with other ligand-bound ErbB family members, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signaling pathways .
ErbB-2 plays a crucial role in cell proliferation, differentiation, and development . It is particularly significant in the context of cancer biology. Amplification or over-expression of the ERBB2 gene has been associated with the development and progression of several aggressive types of cancer, including breast, prostate, ovarian, and lung cancers . Approximately 30% of breast cancer patients exhibit over-expression of HER2, making it an important biomarker and target for therapy .
Recombinant human ErbB-2 is produced using expression systems such as HEK293 cells . The recombinant protein is often tagged (e.g., with a His-tag) to facilitate purification and detection . It is used in various research applications, including studies on receptor-ligand interactions, signal transduction pathways, and the development of therapeutic antibodies .
The clinical significance of ErbB-2 is underscored by the development of targeted therapies such as Trastuzumab (Herceptin), which binds to the extracellular domain of HER2 and inhibits its activity . These therapies have significantly improved the prognosis for patients with HER2-positive cancers .