An anti-oncogenic role for decorin - Down-regulation of ErbB2 leads to growth suppression and cytodifferentiation of mammary carcinoma cells

Citation
M. Santra et al., An anti-oncogenic role for decorin - Down-regulation of ErbB2 leads to growth suppression and cytodifferentiation of mammary carcinoma cells, J BIOL CHEM, 275(45), 2000, pp. 35153-35161
Citations number
67
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
275
Issue
45
Year of publication
2000
Pages
35153 - 35161
Database
ISI
SICI code
0021-9258(20001110)275:45<35153:AARFD->2.0.ZU;2-H
Abstract
The leucine-rich proteoglycan decorin interacts with the epidermal growth f actor receptor and triggers a signaling pathway that leads to growth suppre ssion. We find that decorin causes a functional inactivation of the oncogen ic ErbB2 protein in breast carcinoma cells. Upon de novo expression of deco rin, the ErbB2 protein is reduced by similar to 40%, whereas its degree of tyrosyl phosphorylation is almost completely abrogated. Both co-culture exp eriments or experiments with recombinant decorin demonstrate an initial ind uction of ErbB2 tyrosine kinase, followed by a profound and long-lasting do wnregulation of its activity. This leads to growth inhibition and cytodiffe rentiation of mammary tumor cells and a concurrent suppression of their tum origenic potential in vivo. These decorin-mediated effects appear to involv e the activation of ErbB4, which in turn would block the phosphorylation of heterodimers containing either ErbB2 or ErbB3. These results provide an ex planation for the heightened decorin levels around invasive carcinomas and suggest that decorin may function as a natural antagonist of neoplastic cel ls enriched in ErbB2.