EXPRESSION OF THE C-TERMINUS OF THE AMYLOID PRECURSOR PROTEIN ALTERS GROWTH-FACTOR RESPONSIVENESS IN STABLY TRANSFECTED PC12 CELLS

The amyloid precursor protein (APP) is a molecule centrally involved i n Alzheimer disease pathology, but whose normal function is still poor ly understood, To investigate the consequences of increased intracellu lar production of various regions of APP on cellular physiology, we st ably transfected PC12 cells,vith the C-terminal 100 amino acids of the human APP, In eight transfected clones that express the APP(C100) pro tein, exposure to nerve growth factor (NGF) did not promote differenti ation. Transfectants continued to divide and failed to elaborate exten sive neurites, whereas control PC12 cells, mock-transfected PC12 cells , and a nonexpressing transfected cell line did develop neurites and s topped dividing after NGF stimulation, Unlike NGF treatment, treatment with basic fibroblast growth factor profoundly accelerated neurite ou tgrowth in transfected cells, Also, a dramatic increase in a tyrosine phosphatase activity was noted, Expression and accumulation of APP(C10 0) protein in PC12 cells results in an abnormal response to growth fac tor stimulation.