Molecular Basis of HER-2-Positive Breast Cancer II

– Ligand binding to the HER receptors leads to their homodimerization or heterodimerization, which promotes signal transduction

– 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

– 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), and phospholipase C pathways

– Breast cancer cells and model tumor systems, have shown that over expression of the gene has been associated with increased mitogenesis, malignant transformation, increased cell motility, invasion, and metastasis

– 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

The HER gene family. The proteins are made up of an extracellular ligand-binding domain, a
membrane-sparing region, and a cytoplasmic domain with tyrosine kinase activity. Note that HER-2
has no known ligands. Also note that HER-3 has no intrinsic tyrosine kinase activity.

#Arrangoiz #BreastSurgeon #BreastCancer #CancerSurgeon #SurgicalOncologist #HERPositive #CASO #CenterforAdvancedSurgicalOncology

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