Analysis of representative signaling molecules from pathways downstream of ERBB2 in the tumors. (A) Positive correlation between levels of pERK1/2 (ELISA) and tumor latency. (B) Evaluation of upstream and downstream elements from the ERK1/2 pathway in tumors with short and long latencies. Tumors with a short latency show low levels of pERK1/2 and pMEK and lower levels of KSR1/2. (C) Evaluation of some elements of signaling pathways downstream of ERBB2 in F1BX tumors with and without lung metastases. Tumors that metastasize to the lung show low levels of pAKT(S473). We explored the AKT pathway to clarify this defect (Figure S6A in Additional file 2). This effect was not present in mice with a homogeneous genetic background (Figure S6B in Additional file 2). (D) The main pAKT isoform associated with dissemination to the lung in the F1BX population was pAKT1 (ELISA). (E) Breast tumors of human origin that disseminated show low levels of pAKT compared with those that did not metastasize.