Abstract 1000 Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels in Lung Cancer Cell Media

The transmembrane glycoprotein, amyloid precursor protein (APP) and its processing to amyloid beta (Aβ) are widely recognized for their involvement in Alzheimer's disease and neuronal homeostasis. More recently, research indicates that APP is overexpressed in multiple cancers including lung, promoting cancer cell proliferation. In this study, we set out to identify regulators of soluble amyloid precursor protein α (sAPPα) levels in the media of two human non-small cell lung carcinoma (NSCLC) cells, A549 (p53 wild-type) and H1299 cells (p53-null). Activation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK)1/2, and phosphoinositide 3 Kinase (PI3K) correlated with higher levels of sAPPα, effects that were reversed by treatment with kinase inhibitors and/or upon addition of acetylcholinesterase (AChE) to A549 and H1299 cell media. We also show that increased acetylcholine levels correlated with reduced activities of AChE and p53. Cell viability of A549 and H1299 cells decreased upon co-treatment with AChE and/or PKC, ERK1/2, and PI3K inhibitors.