Cellular effects of HER3-specific affibody molecules
2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 6, e40023- p.Article in journal (Refereed) Published
Recent discoveries have led to the recognition of the epidermal growth factor receptor HER3 as a key player in cancer, and consequently this receptor has gained increased interest as a target for cancer therapy. Although practically devoid of kinase activity, signaling via this receptor is often seen in tumours resistant to EGFR or HER2 therapy. Here, we show that two HER3-specific affibody molecules, Z5416 and Z5417, reduce heregulin-induced cell growth of the breast cancer cells MCF-7 and, to a lesser extent, SKBR‑3 cells. These affibody molecules have earlier been shown to block binding of the natural ligand heregulin (HRG) to HER3, which was confirmed here in cellular studies. Further, both Z5416 and Z5417 blocked HRG-induced HER3 and HER2 phosphorylation in MCF-7 cells, but only HER3 phosphorylation in SKBR-3 cells which have constantly active HER2.. These findings demonstrate that Z5416 and Z5417 exert an anti-proliferative effect on two breast cancer cells with either high or low HER2 expression, by inhibiting HRG-induced phosphorylation of HER3. The promising results presented in this study indicate that the HER3-binding affibody molecules may be suitable candidates for future therapy of cancers in which the interaction between HER3 and HRG plays an important role.
Place, publisher, year, edition, pages
2012. Vol. 7, no 6, e40023- p.
HER3, heregulin, Affibody, proliferation
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-156734DOI: 10.1371/journal.pone.0040023ISI: 000305892100176OAI: oai:DiVA.org:uu-156734DiVA: diva2:433089