ErbB2 dephosphorylation and anti-proliferative effects of neuregulin-1 in ErbB2-overexpressing cells; re-evaluation of their low-affinity interaction.

Abstract

Neuregulin-1 binds to ErbB3 and ErbB4 and regulates cancer proliferation and differentiation. Neuregulin-1 had been suggested to also react with ErbB2, but this argument becomes controversial. Here, we re-evaluated the cellular responses and ErbB2 interaction of neuregulin-1 in ErbB2 overexpressing cell lines. In a competitive ligand-binding assay, we detected significant replacement of [(35)S]-labeled neuregulin-1 with nano molar ranges of cold neuregulin-1 in L929 cells expressing ErbB2 alone and SKOV3 cells carrying sulf-1 cDNA but not in these parental cells. The concentration of neuregulin-1 significantly decreased thymidine incorporation and phosphorylation of ErbB2 (Tyr877, Tyr1396, and Tyr1121) in ErbB2-overexpressing cancer cells as well as in L929 cells expressing ErbB2. A crosslinking assay ascertained the presence of neuregulin-1 immunoreactivity in the ErbB2 immune complexes of L929 expressing ErbB2 alone. These results suggest that the higher concentrations of neuregulin-1 exert an anti-oncogenic activity to attenuate ErbB2 auto-phosphorylation potentially through its low-affinity interaction with ErbB2.

• Authors: Ran Wang, Yuriko Iwakura, Kazuaki Araki, Kazuko Keino-Masu, Masayuki Masu, Xue-yi Wang, Nobuyuki Takei, Shigeki Higashiyama, Hiroyuki Nawa
• Journal: Scientific reports (Sci Rep) Vol. 3 Pg. 1402 ( 2013) ISSN: 2045-2322 [Electronic] England
• PMID: 23466678 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuregulin-1
• Receptor, ErbB-2
• Receptor, ErbB-3

Topics

• Binding, Competitive
• Cell Line
• Cell Proliferation (drug effects)
• Gene Expression
• Humans
• Neuregulin-1 (metabolism, pharmacology)
• Phosphorylation
• Protein Binding
• Receptor, ErbB-2 (genetics, metabolism)
• Receptor, ErbB-3 (genetics, metabolism)