Experimental model construction and validation of the ErbB signaling pathway

The importance of ErbB receptor signaling in breast cancer is consistent with its functional role in normal development of mammary gland. The study of the ErbB signaling network and its bidirectional cross-talk with hormonal receptors, such as estrogen receptor (ER) encloses information about the molecular mechanisms on breast cancer evolution, progression and endocrine resistance. With this analysis we attempt to examine the differences in activation/inhibition of intracellular signaling molecules within ErbB signaling cascade on ER+ and ER-breast cancer patients. With the proposed framework we model the genetic interactions in the ErbB signaling pathway directly from expression data as Gaussian approximations and compare them with the KEGG canonical ErbB pathway in order to identify significant molecular deformations characterizing the studied population. The results indicate a distinct profile of activation/inhibition between the two ER populations and highlight the primary role of PI3K/Akt pathway in breast cancer progression and targeted treatment strategies.