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Open Access 01-12-2016 | Research article

Phosphodiesterases in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia

Authors: Badar Mahmood, Morten Matthiesen Bach Damm, Thorbjørn Søren Rønn Jensen, Marie Balslev Backe, Mattias Salling Dahllöf, Steen Seier Poulsen, Niels Bindslev, Mark Berner Hansen

Published in: BMC Cancer | Issue 1/2016

Abstract

Background

Intracellular signaling through cyclic nucleotides, both cyclic AMP and cyclic GMP, is altered in colorectal cancer. Accordingly, it is hypothesized that an underlying mechanism for colorectal neoplasia involves altered function of phosphodiesterases (PDEs), which affects cyclic nucleotide degradation. Here we present an approach to evaluate the function of selected cyclic nucleotide-PDEs in colonic endoscopic biopsies from non-neoplastic appearing mucosa.

Methods

Biopsies were obtained from patients with and without colorectal neoplasia. Activities of PDEs were characterized functionally by measurements of transepithelial ion transport and their expression and localization by employing real-time qPCR and immunohistochemistry.

Results

In functional studies PDE subtype-4 displayed lower activity in colorectal neoplasia patients (p = 0.006). Furthermore, real-time qPCR analysis showed overexpression of subtype PDE4B (p = 0.002) and subtype PDE5A (p = 0.02) in colorectal neoplasia patients. Finally, immunohistochemistry for 7 PDE isozymes demonstrated the presence of all 7 isozymes, albeit with weak reactions, and with no differences in localization between colorectal neoplasia and control patients. Of note, quantification of PDE subtype immunostaining revealed a lower amount of PDE3A (p = 0.04) and a higher amount of PDE4B (p = 0.02) in samples from colorectal neoplasia patients.

Conclusion

In conclusion, functional data indicated lower activity of PDE4 subtypes while expressional and abundance data indicated a higher expression of PDE4B in patients with colorectal neoplasia. We suggest that cyclic nucleotide-PDE4B is overexpressed as a malfunctioning protein in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia. If a predisposition of reduced PDE4B activity in colonic mucosa from colorectal neoplasia patients is substantiated further, this subtype could be a potential novel early diagnostic risk marker and may even be a target for future medical preventive treatment of colorectal cancer.

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Title: Phosphodiesterases in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia
Authors: Badar Mahmood
Morten Matthiesen Bach Damm
Thorbjørn Søren Rønn Jensen
Marie Balslev Backe
Mattias Salling Dahllöf
Steen Seier Poulsen
Niels Bindslev
Mark Berner Hansen
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-016-2980-z

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