beta-catenin negatively regulates expression of the prostaglandin transporter PGT in the normal intestinal epithelium and colorectal tumour cells: a role in the chemopreventive efficacy of aspirin?
HJM Smartt, A Greenhough, P Ordonez-Moran, M Al-Kharusi, TJ Collard, JM Mariadason, J Huelsken, AC Williams, C Paraskeva
British Journal of Cancer | NATURE PUBLISHING GROUP | Published : 2012
BACKGROUND: Levels of the pro-tumorigenic prostaglandin PGE(2) are increased in colorectal cancer, previously attributed to increased synthesis through COX-2 upregulation and, more recently, to decreased catabolism. The functionally linked genes 15-prostaglandin dehydrogenase (15-PGDH) and the prostaglandin transporter PGT co-operate in prostaglandin degradation and are downregulated in colorectal cancer. We previously reported repression of 15-PGDH expression by the Wnt/β-catenin pathway, commonly deregulated during early colorectal neoplasia. Here we asked whether β-catenin also regulates PGT expression. METHODS: The effect of β-catenin deletion in vivo was addressed by PGT immunostaining ..View full abstract
Awarded by Cancer Research UK
This work was supported by a Programme Grant (C19/A5301) from Cancer Research UK and by the John James Bristol Foundation. We thank Professor Victor Schuster for valuable discussion.