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Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract.

Journal article
Authors Yvonne Arvidsson
Ellinor Andersson
Anders Bergström
Mattias K Andersson
Gülay Altiparmak
Ann-Christin Illerskog-Lindström
Håkan Ahlman
Darima Lamazhapova
Ola Nilsson
Published in Endocrine-related cancer
Volume 15
Issue 2
Pages 569-81
ISSN 1351-0088
Publication year 2008
Published at Institute of Biomedicine, Department of Pathology
Institute of Clinical Sciences
Pages 569-81
Language en
Links dx.doi.org/10.1677/ERC-07-0145
Subject categories Medical and Health Sciences

Abstract

We have examined the global gene expression profile of small intestinal carcinoids by microarray analysis. High expression of a number of genes was found including amyloid precursor-like protein 1 (APLP1). Quantitative real-time PCR and western blot analysis demonstrated higher expression of APLP1 in carcinoid metastases relative to primary tumours indicating a role of APLP1 in tumour dissemination. Tissue microarray analysis of gastroentero-pancreatic tumours demonstrated a high frequency of APLP1 expression and a low frequency of APLP2 expression in neuroendocrine (NE) tumours when compared with non-NE tumours at the same sites. Meta-analysis of gene expression data from a large number of tumours outside the gastrointestinal tract confirmed a correlation between APLP1 expression and NE phenotype where high expression of APLP1 was accompanied by downregulation of APLP2 in NE tumours. Cellular localization of APLP1, APLP2 and amyloid precursor protein (APP) in carcinoid cells (GOT1) by confocal microscopy demonstrated partial co-localization with synaptophysin. This suggests that the APP family of proteins is transported to the cell membrane by synaptic microvesicles and that they may influence tumour cell adhesion and invasiveness. We conclude that APLP1 is differentially upregulated in gastrointestinal NE tumours and that APLP1 may be important for the dissemination of small intestinal carcinoids. Identification of APLP1 in NE tumours offers a novel target for treatment and may also serve as a tumour-specific marker.

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