Loss of c-Jun NH2-Terminal Kinase in Mammary Epithelial Cells is Sufficient for Adenosquamous Tumor Formation

The JNK pathway has been implicated in breast cancer, both from human tumor sequencing studies and from mouse models. To see if JNK deletion is able to form tumors in mice, we crossed Mapk8 and Mapk9 conditional animals with the WAP-Cre expressing mouse to specifically delete JNK in luminal epithelial cells of the breast. We found that JNK suppresses tumors and that the loss of JNK leads to adenosquamous carcinoma formation. To understand the role of JNK in the mammary epithelium, we performed RNA sequencing and analyzed gene expression from tumor-derived cell lines. Several pathways were perturbed in the carcinoma cell lines. Our results demonstrate that loss of JNK alone is sufficient to cause tumor formation and they reveal a gene signature of adenosquamous tumors that can help in better understanding and treating the disease. Overall design: Mammary epithelial cell (control) and adenosquamous tumor cell line expression was analyzed using three independent libraries of each