- The human epidermal receptor (HER) or erbB proteins:
- Are members of the subclass I of the receptor tyrosine kinase superfamily
- This group contains four members:
- Epidermal growth factor receptor (EGFR) / erbB1 / HER-1
- erbB2 / HER-2 / neu
- erbB3 / HER-3
- erbB4 / HER-4
- These proteins are made up of an:
- Extracellular ligand-binding domain
- A membrane-spanning region
- A cytoplasmic domain with tyrosine kinase activity
- Ligand binding to these receptors:
- Leads to their homodimerizartion or heterodimerization:
- Which promotes signal transduction
- Leads to their homodimerizartion or heterodimerization:
- To date, no ligands have been identified for the HER-2 receptor:
- However, the HER-2 receptor has been shown to be the preferred heterodimerization for other HER family members
- This group contains four members:
- Are members of the subclass I of the receptor tyrosine kinase superfamily
Note that HER-2 has no known ligands. Also note that HER-3 has no intrinsic tyrosine kinase activity.
- HER-2 has been shown to be one of the most important oncogenes in human breast cancer
- HER-2 complexes initiate intracellular signaling via the:
- Mitogen-activated protein kinase (MAPK)
- Phosphatidylinositol 3-kinase (PI3K) pathway
- Phospholipase C pathway
- In breast cell lines and model tumor systems:
- Overexpression of the gene has been shown to be associated with:
- Increased mitogenesis
- Malignant transformation
- Increased cell motility
- Invasion
- Metastasis
- Overexpression of the gene has been shown to be associated with:
- In human breast cancer:
- Amplification of the gene is found in around 15% to 30% of primary invasive breast tumors:
- In these cases, up to 100 copies have been demonstrated per cell:
- Which is equivalent to a 50-fold increase in gene copy number per cell
- As a result, the number of receptors per cell is increased up to 2 million
- Overexpression at the messenger RNA or protein level:
- Occurs in around 15% to 30% of patients with early-stage breast cancer
- In these cases, up to 100 copies have been demonstrated per cell:
- Amplification of the gene is found in around 15% to 30% of primary invasive breast tumors:
Rodrigo Arrangoiz MS, MD, FACS, FSSO 