Intestinal-specific PPARγ deficiency enhances tumorigenesis in ApcMin/+ mice
Intestinal-specific PPARγ deficiency enhances tumorigenesis in ApcMin/+ mice
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DOI：
10.1002/ijc.22115
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发表时间：
2006-11-15
影响因子：
6.4
通讯作者：
Cormier, Robert T.
中科院分区：
文献类型：
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作者：
McAlpine, Christen A.;Barak, Yaacov;Cormier, Robert T.
关于过氧化物酶体增殖物激活受体γ (PPAR γ)配体对结肠癌的作用的多项研究产生了相互矛盾的结果。虽然一些研究表明，用各种噻唑烷二酮（TZD） PPAR γ配体治疗的Apc（Min/+）小鼠中结肠息肉数量增加，但其他研究报道了Apc（Min/+）小鼠和化学诱导结肠癌小鼠中肿瘤多样性和进展的改善。在这里，我们利用基因敲除方法研究了PPAR γ在小鼠肠道肿瘤发生中的作用。我们发现杂合子或纯合子肠道特异性PPAR γ缺乏症增加了小肠和结肠中Apc（Min/+）肿瘤的数量，特别是在结肠中，PPAR γ缺乏症也调节了肿瘤的发病率。性别显著影响肿瘤多样性，与pparty基因型无关。雌性Apc（Min/+）小鼠在小肠和总体上出现更多肿瘤，而雄性Apc（Min/+）小鼠在结肠中出现更多肿瘤。然而，无论性别如何，肠道pparty缺乏都会促进肿瘤的发生。我们的研究结果表明，PPAR在小鼠肠道中是一种肿瘤抵抗因子，值得进一步研究PPAR γ依赖性和TZDs在癌症中的独立作用。(c) 2006 Wiley-Liss, Inc。
Multiple investigations of the effects of peroxisome proliferator-activated receptor gamma (PPAR gamma) ligands on colon cancer have produced contradictory results. While some studies demonstrated increased numbers of colonic polyps in Apc(Min/+) mice treated with various thiazolidinedione (TZD) PPAR gamma ligands, others reported amelioration of tumor multiplicity and progression in both Apc(Min/+) mice and in mice with chemically-induced colon cancer. Here, we addressed the role of PPAR gamma in murine intestinal tumorigenesis using gene knockout methodology. We found that either heterozygous or homozygous intestinal-specific PPAR gamma deficiency enhanced the number of Apc(Min/+) tumors in both the small intestine and colon, especially in the colon, where PPAR gamma deficiency also modulated tumor incidence. Gender significantly affected tumor multiplicity independent of PPARy genotype. Female Apc(Min/+) mice developed more tumors in the small intestine and more tumors overall, whereas male Apc(Min/+) mice developed more tumors in the colon. Nevertheless, intestinal PPARy deficiency enhanced tumorigenesis irrespective of gender. Our results suggest that PPARy functions as a tumor resistance factor in the mouse intestine and warrant further investigation of the PPAR gamma-dependent and independent actions of TZDs in cancer. (c) 2006 Wiley-Liss, Inc.