ErbB2, also known as Human Epidermal Growth Factor Receptor-2 (HER2), is a unique member of the ErbB family of receptor tyrosine kinases. It lacks an identified ligand. At normal expression levels, it acts as a shared coreceptor for the ErbB family, with heterodimeric complexes activated by partner ligands. When overexpressed, it can activate kinase through constitutive homodimerization without ligand. The extracellular, transmembrane, and carboxy-terminal domains are necessary for its transactivation [1].

The amplification of the erbB-2 gene leading to protein overexpression is one of the first consistent genetic alterations found in human breast tumors. In multiple myeloma, upregulated expression of ERBB2 mRNA in malignant plasma cells is correlated with poor survival outcomes, including increased cancer mortality, shorter progression-free survival, and worse overall survival [2,3].

In conclusion, ErbB2 plays a crucial role in normal and malignant cell biology, especially in breast cancer and multiple myeloma. Understanding its function through studies on its overexpression and genetic alterations in these diseases can provide insights into cancer pathogenesis, and may guide the development of targeted therapies for these malignancies.

References:

1. Penuel, E, Schaefer, G, Akita, R W, Sliwkowski, M X. . Structural requirements for ErbB2 transactivation. In Seminars in oncology, 28, 36-42. doi:. https://pubmed.ncbi.nlm.nih.gov/11774204/

2. Hynes, N E. . ErbB2 activation and signal transduction in normal and malignant mammary cells. In Journal of mammary gland biology and neoplasia, 1, 199-206. doi:. https://pubmed.ncbi.nlm.nih.gov/10887493/

3. Uckun, Fatih M, Qazi, Sanjive. 2023. Upregulated Expression of ERBB2/HER2 in Multiple Myeloma as a Predictor of Poor Survival Outcomes. In International journal of molecular sciences, 24, . doi:10.3390/ijms24129943. https://pubmed.ncbi.nlm.nih.gov/37373090/