BACKGROUND: 25% of breast cancer patients suffer from aggressive HER2-positive 
tumours that are characterised by overexpression of the HER2 protein or by its 
increased tyrosine kinase activity. Herceptin is a major drug used to treat HER2 
positive breast cancer. Understanding the molecular events that occur when 
breast cancer cells are exposed to Herceptin is therefore of significant 
importance. Dual specificity phosphatases (DUSPs) are central regulators of cell 
signalling that function downstream of HER2, but their role in the cellular 
response to Herceptin is mostly unknown. This study aims to model the initial 
effects of Herceptin exposure on DUSPs in HER2-positive breast cancer cells 
using Boolean modelling.
RESULTS: We experimentally measured expression time courses of 21 different 
DUSPs between 0 and 24 h following Herceptin treatment of human MDA-MB-453 
HER2-positive breast cancer cells. We clustered these time courses into patterns 
of similar dynamics over time. In parallel, we built a series of Boolean models 
representing the known regulatory mechanisms of DUSPs and then demonstrated that 
the dynamics predicted by the models is in agreement with the experimental data. 
Furthermore, we used the models to predict regulatory mechanisms of DUSPs, where 
these mechanisms were partially known.
CONCLUSIONS: Boolean modelling is a powerful technique to investigate and 
understand signalling pathways. We obtained an understanding of different 
regulatory pathways in breast cancer and new insights on how these signalling 
pathways are activated. This method can be generalized to other drugs and longer 
time courses to better understand how resistance to drugs develops in cancer 
cells over time.