The Prostate · 2006 · 66 citations · 39 references
Life SciencesCell BiologyOncologyApoptosisCell SignalingSignal TransductionApoptosis RegulationApoptotic Signal TransductionApoptotic SignalingCancer Cell SignalingProstate CancerTumor Suppressor GenesApoptosis RegulatorsApoptosis Signaling In CancerExtracellular Signal-regulated Kinase PathwayExtracellular Signal-regulated Kinase SignalingJun N-terminal Kinase SignalingPro-apoptotic BalancePro-apoptotic ProteinsTumor Suppressor Loss
BACKGROUND: Although reduced expression levels of annexin I (ANX I) protein is a common finding in all stages of prostate cancer a causative relationship between ANX I dysregulation and prostate cancer development has yet to be established. METHODS: Annexin I expression was restored in LNCaP and MDA PCa 2b that normally express low or undetectable levels of ANX I protein. The impact of restoring ANX I expression on cell viability, colony formation in soft agar, apoptosis, and extracellular signal-regulated kinases (ERK), p38, c-Jun N-terminal kinases (JNK) activation was examined. RESULTS: Restoring ANX I expression reduced cell viability, colony formation, in addition to inducing apoptosis. The proliferative response of epidermal growth factor was blocked by restoring ANX I expression. Furthermore, increasing basal and induced levels of phosphorylated p38 and JNK were observed in prostate cancer cells following restoration of ANX I expression. CONCLUSIONS: Annexin I may have tumor suppressor functions in prostate cancer. The pro-apoptotic effect of ANX I involves the activation of p38 and JNK, which appears to shift the balance of signal transduction away from proliferation and toward apoptosis.
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Requirement of JNK for Stress- Induced Activation of the Cytochrome c-Mediated Death Pathway
Cathy Tournier, Patricia Hess, Derek Yang et al. · Science · 2000 · 1.7K citations