PMID- 9106263 OWN - NLM STAT- MEDLINE DCOM- 19970724 LR - 20190831 IS - 0197-0186 (Print) IS - 0197-0186 (Linking) VI - 30 IP - 4-5 DP - 1997 Apr-May TI - Additive effects of basic fibroblast growth factor and phorbol ester on beta-amyloid precursor protein expression and secretion. PG - 475-81 AB - Expression of the beta-amyloid precursor protein (beta-APP), a proteoglycan whose proteolytically derived fragments have been implicated in the neuropathology observed in Alzheimer's disease, is regulated by a variety of stimuli including cytokines, phorbol esters, and growth factors. In this study we report the effects of basic fibroblast growth factor (bFGF) and the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), on beta-APP expression and secretion in SKNMC human neuroblastoma cells. Treatment of the cells with bFGF for 24 h increased APP promoter activity 200%, cell-associated full-length protein 189%, and secreted amino-terminal fragments 192% compared to basal levels. Treatment of the cells with PMA for 24 h also up-regulated APP expression and secretion with increases of 170, 112, and 161% being observed for promoter activity, cell-associated full-length protein, and secreted amino-terminal fragments, respectively. The effects of bFGF and PMA on the expression and secretion of beta-APP were additive and distinct in that: (a) co-treatment of the cells with maximally stimulating doses of bFGF and PMA had an additive effect on both induced full-length protein expression (242%) and secretion of amino-terminal fragments (311%) compared to basal levels; (b) net levels of full-length protein expression and secretion induced by bFGF and PMA differed significantly from each other; and (c) down-regulation of phorbol ester-stimulated protein kinase C by pre-treatment of the cells for 24 h with 1 microM PMA failed to attenuate bFGF-induced transcription or induced secretion of beta-APP. FAU - Ringheim, G E AU - Ringheim GE AD - Neuroscience Therapeutic Area, Hoechst Marion Roussel Inc., Bridgewater, NJ 08807-0800, USA. FAU - Aschmies, S AU - Aschmies S FAU - Petko, W AU - Petko W LA - eng PT - Journal Article PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Carcinogens) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Amyloid beta-Protein Precursor/*metabolism MH - Blotting, Western MH - Carcinogens/*pharmacology MH - Drug Synergism MH - Enzyme-Linked Immunosorbent Assay MH - Fibroblast Growth Factor 2/*pharmacology MH - Humans MH - Neuroblastoma/metabolism MH - Tetradecanoylphorbol Acetate/*pharmacology MH - Tumor Cells, Cultured EDAT- 1997/04/01 00:00 MHDA- 1997/04/01 00:01 CRDT- 1997/04/01 00:00 PHST- 1997/04/01 00:00 [pubmed] PHST- 1997/04/01 00:01 [medline] PHST- 1997/04/01 00:00 [entrez] AID - 10.1016/s0197-0186(96)00084-8 [doi] PST - ppublish SO - Neurochem Int. 1997 Apr-May;30(4-5):475-81. doi: 10.1016/s0197-0186(96)00084-8.