Increased Expression and Processing of the Alzheimer Amyloid Precursor Protein in Pancreatic Cancer May Influence Cellular Proliferation

Donna E. Hansel, Ayman Rahman, Sven Wehner, Volker Herzog, Charles J. Yeo, Anirban Maitra

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

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 NH2-terminal ectodomain fragment (sAPP), an Aβ 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.

Original languageEnglish (US)
Pages (from-to)7032-7037
Number of pages6
JournalCancer Research
Volume63
Issue number21
StatePublished - Nov 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Increased Expression and Processing of the Alzheimer Amyloid Precursor Protein in Pancreatic Cancer May Influence Cellular Proliferation'. Together they form a unique fingerprint.

Cite this