erbB-2

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Background

erbB-2 is a transmembrane, tyrosine kinase (TK) receptor whose overexpression is associated with adverse prognosis in breast cancer1.
The human epidermal growth factor receptor (erbB-2) is a transmembrane receptor that is overexpressed in 15%–25% of breast cancers. erbB-2 overactivity is associated with adverse biological characteristics and poor clinical outcomes1.Overexpression of erbB2 in cell lines leads to transformation in the absence of a ligand2. None of the EGF family of ligands binds to ErbB2 directly. Therefore, in a technical sense, ErbB2 remains an orphan receptor.
A wide variety of human tumors contain an amplified or overexpressed erbB-2 gene, which encodes a growth factor receptor-like protein. When erbB-2 complementary DNA was expressed in NIH/3T3 cells under the control of the SV40 promoter, the gene lacked transforming activity despite expression of detectable levels of the erbB-2 protein. A further five- to tenfold increase in its expression under influence of the long terminal repeat of Moloney murine leukemia virus was associated with activation of erbB-2 as a potent oncogene. The high levels of the erbB-2 product associated with malignant transformation of NIH/3T3 cells were observed in human mammary tumor cells that overexpressed this gene3.

1. V. Roy, E. A. Perez. Beyond Trastuzumab: Small Molecule Tyrosine Kinase Inhibitors in HER-2–Positive Breast Cancer The Oncologist 2009;14:1061–1069
2. Di Fiore PP, Pierce JH, Fleming TP, Hazan R, Ullrich A, King CR, Schlessinger J, Aaronson SA: Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells. Cell 1987, 51:1063-1070.
3. P.P. Di Fiore, J. H. Pierce, M. H. Kraus, O. Segatto, C. R. King, S. A. Aaronson. erbB-2 is a Potent Oncogene When Overexpressed in NIH/3T3 Cells. Science, New Series, 237: 178-182