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HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. But contrary to other members of the ERBB family, HER2 does not directly bind ligand. HER2 activation results from heterodimerization with another ERBB member or by homodimerization when HER2 concentration are high, for instance in cancer. [8]
These downstream signaling proteins initiate several signal transduction cascades, principally the MAPK, Akt and JNK pathways, leading to DNA synthesis and cell proliferation. [12] Such proteins modulate phenotypes such as cell migration, adhesion, and proliferation. Activation of the receptor is important for the innate immune response in ...
HER2 is an established therapeutic target within breast cancer, and the activation of HER2 is observed in approximately 20% of breast cancers as a result of overexpression. [ 19 ] [ 20 ] Trastuzumab , the first HER2-targeted drug developed in 1990, interferes with HER2 signalling.
The Ras-Raf-MAPK pathway is a major signalling route for the ErbB family, as is the PI3-K/AKT pathway, both of which lead to increased cell proliferation and inhibition of apoptosis. [ 25 ] Genetic Ras mutations are infrequent in breast cancer but Ras may be pathologically activated in breast cancer by overexpression of ErbB receptors. [ 26 ]
MAPK/ERK pathway: A pathway that couples intracellular responses to the binding of growth factors to cell surface receptors. This pathway is very complex and includes many protein components. [53] In many cell types, activation of this pathway promotes cell division, and many forms of cancer are associated with aberrations in it. [54]
The human ERBB3 gene is located on the long arm of chromosome 12 (12q13). It is encoded by 23,651 base pairs and translates into 1342 amino acids. [5]During human development, ERBB3 is expressed in skin, bone, muscle, nervous system, heart, lungs, and intestinal epithelium. [6]
Luminal B (ER and/or PR positive; HER2 positive) HER2-enriched (ER/PR negative; HER2 positive) Basal like (triple negative). [6] Additionally, cancers can be ER-/PR+ or ER+/PR-, but these are unnamed and relatively rare. [7] The receptor status of a cancer is assessed for all breast cancers as it has important implications on prognosis of the ...
Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain. Grb2 has two closely related proteins with similar domain organizations, Gads and Grap.