Mutoh Michihiro, Komiya Masami, Teraoka Naoya, Ueno Toshiya, Takahashi Mami, Kitahashi Tsukasa, Sugimura Takashi, Wakabayashi Keiji
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Tokyo, Japan.
Int J Cancer. 2009 Dec 1;125(11):2505-10. doi: 10.1002/ijc.24667.
Apc-deficient Min mice feature low expression of lipoprotein lipase (LPL), high concentration of serum triglyceride (TG), fatty change of the liver and large numbers of intestinal polyps. We have reported that induction of LPL expression reduces serum lipid, especially TG, improves fatty change of the liver and inhibits intestinal polyp formation in the mice. In this study, fatty change/lipid accumulation in intestinal mucosa and polyps in Min mice were analyzed by Oil-red O staining and electron microscopy. A number of large lipid droplets were found in the epithelia of the upper part of polyps. On the other hand, small lipid droplets were only slightly observed at the tip of the villi in non-tumoros parts of the small intestine of Min mice and in the villi of wild-type mice. Moreover, low-density lipoprotein receptor (LDLR) was overexpressed in the area where lipid droplets were observed. The expression levels of LDLR mRNA in the intestinal polyps of Min mice were approximately 3 times higher compared to those in the non-tumoros parts. Remarkable expression of cyclooxygenase-2 was mainly distributed in stromal cells and some in epithelial cells. It is speculated that lipid accumulation in the intestinal polyps may play an important role in intestinal polyp formation in Apc-deficient mice.
Apc基因缺陷的Min小鼠具有脂蛋白脂肪酶(LPL)表达低、血清甘油三酯(TG)浓度高、肝脏脂肪变性以及大量肠息肉的特征。我们曾报道,诱导LPL表达可降低血清脂质,尤其是TG,改善肝脏脂肪变性并抑制小鼠肠息肉形成。在本研究中,通过油红O染色和电子显微镜分析了Min小鼠肠黏膜和息肉中的脂肪变性/脂质蓄积情况。在息肉上部的上皮细胞中发现了许多大脂滴。另一方面,在Min小鼠小肠非肿瘤部位的绒毛尖端以及野生型小鼠的绒毛中仅轻微观察到小脂滴。此外,在观察到脂滴的区域低密度脂蛋白受体(LDLR)过表达。Min小鼠肠息肉中LDLR mRNA的表达水平比非肿瘤部位高约3倍。环氧化酶-2的显著表达主要分布在基质细胞中,部分分布在上皮细胞中。推测肠息肉中的脂质蓄积可能在Apc基因缺陷小鼠的肠息肉形成中起重要作用。