| First Author | Zuo X | Year | 2012 |
| Journal | J Natl Cancer Inst | Volume | 104 |
| Issue | 9 | Pages | 709-16 |
| PubMed ID | 22472308 | Mgi Jnum | J:185724 |
| Mgi Id | MGI:5429787 | Doi | 10.1093/jnci/djs187 |
| Citation | Zuo X, et al. (2012) Effects of gut-targeted 15-LOX-1 transgene expression on colonic tumorigenesis in mice. J Natl Cancer Inst 104(9):709-16 |
| abstractText | Expression of 15-lipoxygenase-1 (15-LOX-1) is decreased in many human cancers; however, the mechanistic significance of its decreased expression has been difficult to determine because its mouse homolog 12/15-LOX has opposing functions. We generated a mouse model in which expression of a human 15-LOX-1 transgene was targeted to the intestinal epithelium via the villin promoter. Targeted expression was confirmed by real-time reverse transcription-polymerase chain reaction and immunoblotting. When the 15-LOX-1 transgene was expressed in colonic epithelial cells of two independent mouse lines (B6 and FVB), azoxymethane-inducible colonic tumorigenesis was suppressed (mean number of tumors: wild type [WT] = 8.2, 15-LOX-1(+/-) = 4.91, 15-LOX-1(+/+) = 3.57; WT vs 15-LOX-1(+/-) two-sided P = .003, WT vs 15-LOX-1(+/+) two-sided P < .001; n = 10-14 mice per group). 15-LOX-1 transgene expression was always decreased in the tumors that did develop. In the presence of expression of the 15-LOX-1 transgene, expression of tumor necrosis factor alpha and its target inducible nitric oxide synthase were decreased and activation of nuclear factor-kappa B in colonic epithelial cells was inhibited. |
