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The MAPK extracellular signal-regulated kinase (ERK1/2) has been implicated in many processes involved in tumor progression, including proliferation, survival, migration, and invasion. We have reported previously that serum and epidermal growth factor (EGF) synergistically promote breast cancer cell invasion. Using various inhibitors, we observed that EGF stimulated breast cancer cell invasion through ERK1/2, which was suppressed by the JNK inhibitor SP600125, but not the p38 MAPK inhibitor SB203580. Consistent with this observation, EGF activated the JNK-dependent transcription factor c-Jun and led to phosphorylation of ERK1/2 and induction of the AP-1 family members c-Fos and c-Jun, both of which are necessary for EGF-induced invasion. The MAPK/ERK pathway inhibitor PD98059, but not the JNK inhibitor SP600125, suppressed invasion stimulated by EGF and serum. This suggests that, in contrast to the effect of serum on invasiveness, EGF-induced invasion is mediated by a JNK-dependent pathway, which is activated downstream of ERK. Finally, using a dominant-negative form of c-Jun, we show that only ERK1/2 but not p38 plays an essential role in EGF-induced invasion. In this way, EGF stimulates invasion by increasing phosphorylation of ERK1/2 via JNK.Television Guide
Get ready for a “murder mystery of the century.” Murder, She Wrote, the true-to-life series in which former newspaper reporter Jessica Fletcher investigates a crime while accompanied by her witty and wisecracking sidekick, is back!
The two-hour premiere episode, titled “Murder on Tea Time” airs Sunday, March 19, at 10 p.m. on CBS.