Activation of mitogen-activated protein kinase associated with prostate cancer progression

Using an antibody specific for dually phosphorylated extracellular-regulate d kinases 1 and 2, we have examined 82 primary and metastatic prostate tumo r specimens for the presence of activated mitogen-activated protein (MAP) k inase, Nonneoplastic prostate tissue showed little or no staining with acti vated MAP kinase antiserum. In prostate tumors, the level of activated MAP kinase increased with increasing Gleason score and tumor stage. In a separa te analysis, tumor samples from two patients showed no activation of MAP ki nase before androgen ablation therapy; however, following androgen ablation treatment, high levels of activated MAP kinase were detected in the recurr ent tumors. Collectively, these data suggest an increase in the activation of the MAP kinase signal transduction pathway as prostate cancer progresses to a more advanced and androgen-independent disease.