Address of Corresponding Author

Tumor Biol 2006;27:201-210 (DOI: 10.1159/000093023)

  Key Words

• Affibody
• Akt
• Erk
• HER2
• PLC1
• Signal transduction

  Abstract

Background: HER2, which is overexpressed in 25-30% of human breast cancers, is a tyrosine kinase receptor critical for the signal transduction network that regulates proliferation, migration and apoptosis of cells. Method: We report the effects of two novel HER2-binding affibody molecules (Affibody^®), (Z_HER2:4)₂ and Z_HER2:342, on intracellular signal transduction pathways (Erk1/2, Akt and PLC1) using quantitative immunoblotting techniques and their biological effects in cell culture. The clinically approved antibody trastuzumab (Herceptin^®) was used as reference substance. Results: Our data showed that, although all substances target HER2, the effects on the receptor and signaling molecules differed. For example, HER2 phosphorylation was induced by trastuzumab and (Z_HER2:4)₂ but inhibited by Z_HER2:342. The effects these substances had on signal transduction correlated to some degree with changes in growth and migration, e.g. (Z_HER2:4)₂ stimulated phosphorylation of Erk1/2 and PLC1, as well as growth and migration, while Z_HER2:342 did not. Z_HER2:342 even inhibited phosphorylation of PLC1 and migration. Conclusion: Our data suggest that Z_HER2:342 is a promising small agent (7 kDa) that may be used as an alternative, or complement, to trastuzumab. If radiolabelled, it can hopefully also be used for HER2 imaging and radionuclide therapy.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Johan Lennartsson
Ludwig Institute for Cancer Research, Uppsala University
Box 595, Biomedical Center
SE-751 24 Uppsala (Sweden)
Tel. +46 18 160406, Fax +46 18 160420, E-Mail Johan.Lennartsson@LICR.uu.se

  Article Information

Received: July 30, 2005
Accepted after revision: October 27, 2005
Published online: April 27, 2006
Number of Print Pages : 10
Number of Figures : 7, Number of Tables : 2, Number of References : 28