Herceptin Research Today is a free monthly online journal that collates and summarizes the latest research about Herceptin, including details on side-effects, breast cancer, treatment, therapy.

Associations of ErbB2, beta1-integrin and lipid rafts on Herceptin (Trastuzumab) resistant and sensitive tumor cell lines.

Mocanu MM, Fazekas Z, Petrás M, Nagy P, Sebestyén Z, Isola J, Tímár J, Park JW, Vereb G, Szöllosi J

Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, P.O. Box 39, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.

ErbB2-mediated transmembrane signaling is a key target of novel anticancer agents such as Herceptin. Our comparison of Herceptin resistant (JIMT-1, MKN-7) and sensitive (SKBR-3, N-87) cell lines demonstrates the importance of ErbB2 association patterns involving integrins and lipid rafts. Flow cytometric FRET and confocal microscopic measurements revealed colocalization and molecular proximity between beta1-integrins and ErbB2, as well as their association with lipid rafts. A weak functional interaction between ErbB2 and beta1-integrin and the fact that ErbB2 did not co-patch with beta1-integrins upon crosslinking imply that ErbB2 and beta1-integrin define two distinct molecular association clusters from a functional point of view. Although Herceptin-sensitive cell lines expressed more ErbB2 and fewer beta1-integrin molecules on their surface than their resistant counterparts, this finding probably does not explain the Herceptin resistant phenotype due to the weak interaction between beta1-integrins and ErbB2. Our results imply that the true significance of the expression profile of proteins involved in oncogenesis can only be understood after characterizing their molecular interactions.

Published 22 August 2005 in Cancer Lett, 227(2): 201-12.
Full-text of this article is available online (may require subscription).

© 2004-2008 Herceptin Research Today. All Rights Reserved.