Dissociation between growth arrest and differentiation in Caco-2 subclone expressing high levels of sucrase.

Dissociation between growth arrest and differentiation in Caco-2 subclone expressing high levels of sucrase.
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表达高水平蔗糖酶的 Caco-2 亚克隆中生长停滞和分化之间的分离。

DOI:
10.1152/ajpgi.1999.276.5.g1094
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发表时间:
1999
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
Quaroni,A
Quaroni,A
中科院分区:
--
文献类型:
--
作者:
Tian,JQ;Quaroni,A

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生长停滞和细胞分化通常被认为是小肠隐窝细胞和结肠肿瘤细胞系在时间和功能上相关的现象(Caco-2, HT-29)。我们已经得到了一个Caco-2亚克隆(NGI3),它偏离了这种范式。与亲代细胞形成鲜明对比的是,增殖和亚融合的NGI3细胞表达蔗糖-异麦芽糖酶(SI) mRNA,并合成相对较高水平的SI、二肽基肽酶IV和氨基肽酶N (APN)。在融合后的细胞中,Caco-2和NGI3细胞之间的SI mRNA水平差异不大,但后者表达的SI水平仍然高得多,这可能归因于更高的翻译率。APN在NGI3细胞中的表达也显著增强。为了确定高水平的刷边酶是否与细胞周期调节蛋白的表达相关,我们研究了它们在生长细胞和生长停滞细胞中的相对细胞水平。结果表明,细胞周期蛋白依赖性激酶抑制剂(p21和p27)和d型细胞周期蛋白(D1和D3)均可在融合后细胞中诱导表达,但NGI3细胞表达的p21水平更高。本研究表明,在肠上皮细胞中,细胞生长和分化性状的表达并不相互排斥,并提供证据表明转录后事件在SI表达调控中起重要作用。
Growth arrest and cell differentiation are generally considered temporally and functionally linked phenomena in small intestinal crypt cells and colon tumor cell lines (Caco-2, HT-29). We have derived a Caco-2 subclone (NGI3) that deviates from such a paradigm. In striking contrast with the parental cells, proliferative and subconfluent NGI3 cells were found to express sucrase-isomaltase (SI) mRNA and to synthesize relatively high levels of SI, dipeptidyl peptidase IV, and aminopeptidase N (APN). In postconfluent cells, little difference was seen in SI mRNA levels between Caco-2 and NGI3 cells, but the latter still expressed much higher levels of SI that could be attributed to higher rates of translation. APN expression was also greatly enhanced in NGI3 cells. To determine whether high levels of brush-border enzymes correlated with expression of cell-cycle regulatory proteins, we investigated their relative cellular levels in growing and growth-arrested cells. The results showed that the cyclin-dependent kinase inhibitors (p21 and p27) and D-type cyclins (D1 and D3) were all induced in postconfluent cells, but NGI3 cells expressed much higher levels of p21. This study demonstrated that cell growth and expression of differentiated traits are not mutually exclusive in intestinal epithelial cells and provided evidence indicating that posttranscriptional events play an important role in regulation of SI expression.
肠隐窝和绒毛细胞中蔗糖酶-异麦芽酶表达的翻译后调节。
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