Effects of gut-targeted 15-LOX-1 transgene expression on colonic tumorigenesis in mice.
Effects of gut-targeted 15-LOX-1 transgene expression on colonic tumorigenesis in mice.
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DOI：
10.1093/jnci/djs187
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发表时间：
2012-05
期刊：
影响因子：
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通讯作者：
Xiangsheng Zuo;Zhanglong Peng;Yuanqing Wu;M. Moussalli;Xiu L Yang;Yan Wang;J. Parker-Thornburg;Jeffrey S. Morris;R. Broaddus;S. Fischer;I. Shureiqi
中科院分区：
文献类型：
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作者：
Xiangsheng Zuo;Zhanglong Peng;Yuanqing Wu;M. Moussalli;Xiu L Yang;Yan Wang;J. Parker-Thornburg;Jeffrey S. Morris;R. Broaddus;S. Fischer;I. Shureiqi
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.
