Lack of guanylyl cyclase C, the receptor for Escherichia coli heat-stable enterotoxin, results in reduced polyp formation and increased apoptosis in the multiple intestinal neoplasia (Min) mouse model.
Lack of guanylyl cyclase C, the receptor for Escherichia coli heat-stable enterotoxin, results in reduced polyp formation and increased apoptosis in the multiple intestinal neoplasia (Min) mouse model.
复制标题
在多发性肠道肿瘤 (Min) 小鼠模型中，缺乏鸟苷酸环化酶 C（大肠杆菌热稳定肠毒素的受体）会导致息肉形成减少和细胞凋亡增加。
DOI：
10.1002/ijc.21119
复制
发表时间：
2005
影响因子：
6.4
通讯作者：
Giannella,RalphA
中科院分区：
文献类型：
--
作者：
Mann,ElizabethA;Steinbrecher,KrisA;Stroup,Carmen;Witte,DavidP;Cohen,MitchellB;Giannella,RalphA
鸟苷酸环化酶C（GC-C）是细菌热稳定肠毒素和哺乳动物肽鸟苷素和尿鸟苷素的跨膜受体，介导肠离子分泌并通过环GMP信号传导影响肠细胞生长。在肠肿瘤中，GC-C表达维持，而鸟苷素和尿鸟苷素表达丢失，表明GC-C活化在肿瘤形成或生长中的作用。我们通过原位杂交表明，GC‐C表达保留在多发性肠肿瘤（ApcMin/+）小鼠的腺瘤中。为了确定GC-C在肠道肿瘤发生中的体内作用，我们产生了编码GC-C基因的靶向缺失纯合子ApcMin/+小鼠，并假设这些小鼠与相同遗传背景的野生型ApcMin/+小鼠相比，肿瘤多样性和大小增加。相比之下，GC-C的缺失导致中位息肉数量减少55%。息肉的中位直径没有变化，表明对肿瘤生长没有影响。野生型Apcallele的体细胞丢失是肠道肿瘤发生的起始事件，也发生在GC-C-缺陷ApcMin/+小鼠的息肉中。我们发现，与ApcMin/+小鼠相比，GC-C-deficientApcMin/+小鼠肠道中细胞凋亡水平增加，caspase-3和caspase-7基因表达增加。我们认为这些改变是一种可能的补偿机制，通过这种机制，GC‐C信号的丢失也会影响肿瘤的发生。2005年出版Wiley利斯公司
Guanylyl cyclase C (GC‐C), a transmembrane receptor for bacterial heat‐stable enterotoxin and the mammalian peptides guanylin and uroguanylin, mediates intestinal ion secretion and affects intestinal cell growth via cyclic GMP signaling. In intestinal tumors, GC‐C expression is maintained while guanylin and uroguanylin expression is lost, suggesting a role for GC‐C activation in tumor formation or growth. We show byin situhybridization that GC‐C expression is retained in adenomas from multiple intestinal neoplasia (ApcMin/+) mice. In order to determine thein vivorole of GC‐C in intestinal tumorigenesis, we generatedApcMin/+mice homozygous for a targeted deletion of the gene encoding GC‐C and hypothesized that these mice would have increased tumor multiplicity and size compared to wild‐typeApcMin/+mice on the same genetic background. In contrast, the absence of GC‐C resulted in a reduction of median polyp number by 55%. There was no change in the median diameter of polyps, suggesting no effect on tumor growth. Somatic loss of the wild‐typeApcallele, an initiating event in intestinal tumorigenesis, also occurred in polyps from GC‐C‐deficientApcMin/+mice. We have found increased levels of apoptosis as well as increased caspase‐3 and caspase‐7 gene expression in the intestines of GC‐C‐deficientApcMin/+mice compared withApcMin/+mice. We propose that these alterations are a possible compensatory mechanism by which loss of GC‐C signaling also affects tumorigenesis. Published 2005 Wiley‐Liss, Inc.