Ln. Klapper et al., The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors, P NAS US, 96(9), 1999, pp. 4995-5000
Citations number
40
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
The erbB-2/HER2 oncogene is overexpressed in a significant fraction of huma
n carcinomas of the breast, ovary, and lung in a manner that correlates wit
h poor prognosis. Although the encoded protein resembles several receptors
for growth factors, no high affinity ligand of ErbB-2 has so far been fully
characterized. However, several lines of evidence have raised the possibil
ity that ErbB-2 can augment signal transduction initiated by binding of cer
tain growth factors to their direct receptors. Here, we contrasted these tw
o models of ErbB-2 function: First, examination of a large series of epider
mal growth factor (EGF)-like ligands and neuregulins, including virus-encod
ed ligands as well as related motifs derived from the precursor of EGF, fai
led to detect interactions with ErbB-2 when this protein,vas singly express
ed. Second, by using antibodies that block inter-ErbB interactions and cell
s devoid of surface ErbB-2, we learned that signaling by all ligands examin
ed, except those derived from the precursor of EGF, was enhanced by the onc
oprotein. These results imply that ErbB-2 evolved as a shared receptor subu
nit of all ErbB-specific growth factors. Thus, oncogenicity of ErbB-2 in hu
man epithelia may not rely on the existence of a specific ligand but rather
on its ability to act as a coreceptor for multiple stroma-derived growth f
actors.