Overexpression of ERBB2 (HER2), usually as a consequence of ERBB2 gene amplification, results in formation of ERBB2 homodimers. Under normal conditions, only ERBB2 heterodimers form, as ERBB2 is expressed at low levels.
ERBB2 homodimerization leads to activation of ERBB2 signaling in the absence of growth factors. Signaling by ERBB2 homodimers mainly activates the RAS/RAF/MAPK signaling cascade, while PI3K/AKT signaling is not significantly affected (Pickl and Ries 2009).
Trastuzumab (Herceptin), a recombinant antibody clinically approved as an anti-cancer therapeutic for ERBB2-overexpressing cancers, preferentially binds to ERBB2 homodimers (Pickl and Ries 2009).
Accurate functional analysis of ERBB2 signaling may require 3D instead of 2D cell culture (Pickl and Ries 2009).