| First Author | Backlund MG | Year | 2008 |
| Journal | Cancer Res | Volume | 68 |
| Issue | 22 | Pages | 9331-7 |
| PubMed ID | 19010907 | Mgi Jnum | J:141385 |
| Mgi Id | MGI:3818199 | Doi | 10.1158/0008-5472.CAN-08-2893 |
| Citation | Backlund MG, et al. (2008) Repression of 15-hydroxyprostaglandin dehydrogenase involves histone deacetylase 2 and snail in colorectal cancer. Cancer Res 68(22):9331-7 |
| abstractText | Prostaglandin E(2) (PGE(2)) promotes cancer progression by modulating proliferation, apoptosis, angiogenesis, and the immune response. Enzymatic degradation of PGE(2) involves the NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Recent reports have shown a marked diminution of 15-PGDH expression in colorectal carcinomas (CRC). We report here that treatment of CRC cells with histone deacetylase (HDAC) inhibitors, including sodium butyrate and valproic acid, induces 15-PGDH expression. Additionally, we show that pretreatment of CRC cells with HDAC inhibitors can block epidermal growth factor-mediated or Snail-mediated transcriptional repression of 15-PGDH. We show an interaction between Snail and HDAC2 and the binding of HDAC2 to the 15-PGDH promoter. In vivo, we observe increased Hdac2 expression in Apc-deficient mouse adenomas, which inversely correlated with loss of 15-Pgdh expression. Finally, in human colon cancers, elevated HDAC expression correlated with down-regulation of 15-PGDH. These data suggest that class I HDACs, specifically HDAC2, and the transcriptional repressor Snail play a central role in the suppression of 15-PGDH expression. These results also provide a cyclooxygenase-2-independent mechanism to explain increased PGE(2) levels that contribute to progression of CRC. |
