| First Author | Ustyugova IV | Year | 2012 |
| Journal | Mol Cancer Res | Volume | 10 |
| Issue | 6 | Pages | 760-7 |
| PubMed ID | 22550081 | Mgi Jnum | J:194587 |
| Mgi Id | MGI:5474303 | Doi | 10.1158/1541-7786.MCR-11-0556 |
| Citation | Ustyugova IV, et al. (2012) IEX-1 deficiency protects against colonic cancer. Mol Cancer Res 10(6):760-7 |
| abstractText | The immediate early response gene X-1 (IEX-1) is involved in regulation of various cellular processes including proliferation, apoptosis in part by controlling homeostasis of reactive oxygen species (ROS) at mitochondria. The present study shows reduced inflammatory responses and colorectal cancer in IEX-1 knockout (KO) mice treated with azoxymethane/dextran sulfate sodium (DSS). However, DSS induced worse colitis in RAG(-/-)IEX-1(-/-) double KO mice than in RAG and IEX-1 single KO mice, underscoring an importance of T cells in IEX-1 deficiency-induced protection against colon inflammation. Lack of IEX-1 promoted the differentiation of interleukin (IL)-17-producing T cells, concomitant with upregulation of Galphai2 expression, a gene that is well-documented for its role in the control of inflammation in the colon. In accordance with this, T-helper 17 (T(H)17) cell differentiation was compromised in the absence of Galphai2, and deletion of Galphai2 in T cells alone aggravated colon inflammation and colorectal cancer development after azoxymethane/DSS treatment. Null mutation of IEX-1 also enhanced both proliferation and apoptosis of intestinal epithelial cells (IEC) after injury. A potential impact of this altered IEC turnover on colon inflammation and cancer development is discussed. These observations provide a linkage of IEX-1 and Galphai2 expression in the regulation of T(H)17 cell differentiation and suggest a previously unappreciated role for IEX-1 in the control of colon epithelial homeostasis. |
