C-Jun N-Terminal Kinase and Apoptosis in Breast Cancer

摘要

Understanding the biochemical mechanisms of apoptosis is important for revealing cancer biology and for improving cancer therapies. The c-Jun N- terminal kinase (JNK) pathway participates in cellular responses to both environmental stresses and mitogenic signals. JNK is involved in cellular signaling during apoptosis induced by various agents including gamma-radiation, UV-radiation, anti-carcinogenic isothiocyanates, and retinoid analog N-(4- hydroxyphenyl) retinamide (4-HPR) in various cancer cells. Interfering with the JNK pathway suppressed the induction of apoptosis. JNK activation by apoptotic stimuli can be caspase-dependent or independent. Different apoptotic stimuli induce JNK activation through distinct mechanisms. We found that oxidative stress is a major cause of JNK activation in apoptosis induced by several agents. The involvement of JNK in both mitogenic and apoptotic signaling implies that a subtle regulatory mechanism must exist for the signaling decision. Our studies reveal that the duration of JNK induction may determine cell fate. Curcumin is a potent inhibitor for JNK activation by various stimuli. This inhibitory effect may explain the anti-carcinogenic effect of curcumin. In conclusion, our study reveals the importance of the JNK pathway in apoptotic signaling. These results provide important information for the studies of oncogenesis and the mechanisms of radiation and drug resistance in cancer cells.