| First Author | Smartt HJ | Year | 2012 |
| Journal | Br J Cancer | Volume | 107 |
| Issue | 9 | Pages | 1514-7 |
| PubMed ID | 23033009 | Mgi Jnum | J:193654 |
| Mgi Id | MGI:5468903 | Doi | 10.1038/bjc.2012.430 |
| Citation | Smartt HJ, et al. (2012) 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?. Br J Cancer 107(9):1514-7 |
| abstractText | 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/beta-catenin pathway, commonly deregulated during early colorectal neoplasia. Here we asked whether beta-catenin also regulates PGT expression. METHODS: The effect of beta-catenin deletion in vivo was addressed by PGT immunostaining of beta-catenin(-/lox)-villin-cre-ERT2 mouse tissue. The effect of siRNA-mediated beta-catenin knockdown and dnTCF4 induction in vitro was addressed by semi-quantitative and quantitative real-time RT-PCR and immunoblotting. RESULTS: This study shows for the first time that deletion of beta-catenin in murine intestinal epithelium in vivo upregulates PGT protein, especially in the crypt epithelium. Furthermore, beta-catenin knockdown in vitro increases PGT expression in both colorectal adenoma- and carcinoma-derived cell lines, as does dnTCF4 induction in LS174T cells. CONCLUSIONS: These data suggest that beta-catenin employs a two-pronged approach to inhibiting prostaglandin turnover during colorectal neoplasia by repressing PGT expression in addition to 15-PGDH. Furthermore, our data highlight a potential mechanism that may contribute to the non-selective NSAID aspirin's chemopreventive efficacy. |
