In this study, we screened out a non-classical PKCδ/MAPK/ERK signaling pathway involved in EGF-induced PN-1 up-regulation in breast cancer cells, first provided the evidence that PN-1 could be up-regulated by EGF/EGFR/PKCδ/MEK/ERK signaling pathway. This evidence concerns the gene SERPINE2 and breast cancer.