Reciprocal changes in p27(Kip1) and p21(Cip1) in growth inhibition mediated by blockade or overstimulation of epidermal growth factor receptors.

作者: Zhen Fan , Jia Ling Chou , Yang Lu , Barbara Y. Shang , John Mendelsohn

DOI:

关键词: Epidermoid carcinomaReceptorGrowth inhibitionCell growthInternal medicineBiologyEpidermal growth factorCell biologyEndocrinologyStimulationMechanism of actionA431 cells

摘要: Many human epithelial tumors express high levels of epidermal growth factor (EGF) receptors. A human-mouse chimeric version anti-EGF receptor monoclonal antibody (mAb) C225, which blocks activation and produces inhibition cell proliferation, is currently being investigated in clinical trials. When cells bear numbers EGF receptors, either complete blockade receptors with mAb 225 or full results proliferation. In the present study, we have explored molecular mechanisms explaining how a inhibitor, 225, activator, EGF, can both produce A431 squamous carcinoma cells. We reported previously that by associated up-regulation p21(Cip1). now demonstrate 255-mediated p27(Kip1), binds to inactivates cyclin-dependent kinase-2 activity cycle arrest G1. Furthermore, be overcome titrating cultures increasing concentrations accompanied concurrent fall level p27(Kip1). At properly titrated inhibitory activities are counterbalanced abolished. reach enough compete near-saturating activation, p27(Kip1) falls below basal levels; however, concomitant marked rise p21(Cip1) inhibition. Our data suggest although induced act independently, they play reciprocal roles mediating saturating EGF.

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