Increased expression and processing of the Alzheimer amyloid precursor protein in pancreatic cancer may influence cellular proliferation.
Abnormal cleavage of amyloid precursor protein (APP) in the central nervous system has been linked to the development of Alzheimer's disease. Recent work has identified additional roles for APP in peripheral tissue, such as cellular proliferation and motility. APP undergoes proteolytic processing to release a soluble NH(2)-terminal ectodomain fragment (sAPP), an Abeta or p3 peptide, and cytosolic COOH-terminal fragments. We have identified the up-regulation of APP expression in pancreatic cancer cells both in vitro and in vivo. APP undergoes high levels of proteolytic processing in pancreatic cancer cells, and sAPP can be detected in collected medium in vitro. Inhibition of sAPP signaling reduces pancreatic cancer cell number via a reduction in cellular proliferation. We propose that APP may function to promote growth in pancreatic cancer cells via signaling through sAPP and may therefore represent a novel therapeutic target in pancreatic cancer.
Hansel
Donna E
DE
Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA. dhansel@jhmi.edu
Rahman
Ayman
A
Wehner
Sven
S
Herzog
Volker
V
Yeo
Charles J
CJ
Maitra
Anirban
A
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016564:Amyloid beta-Protein Precursor