Background: Downstream signaling is a key component of Her2/neu overexpression in human breast cancer. Major survival pathways downstream of Her2/neu include mitogen and stress activated protein kinases (ERK, JNK, p38).
Materials and methods: MAPK protein expression was examined in mouse and human cancer tissue. MAPK expression was inhibited by genetic and pharmacologic methods in human breast cancer cell lines. The effects of MAPK inhibition on tumor formation in a preclinical model were determined.
Results: It was shown that tumors from MMTV-neu mice expressed high levels of activated JNK1. Levels of this kinase were also highest in Her2/neu overexpressing human breast cancer cell lines. JNK1 inhibition specifically induced apoptosis in these lines. A JNK1 inhibitor also increased the latency period and decreased growth of MMTV-neu tumors by induction of apoptosis. JNK1 was preferentially activated in human breast cancer tissue overexpressing Her2/neu.
Conclusion: JNK1 promotes cell survival in Her2/neu-positive breast cancer.