INHIBITION OF SUCRASE-ISOMALTASE EXPRESSION BY EGF IN THE HUMAN COLON ADENOCARCINOMA CELLS CACO-2
INHIBITION OF SUCRASE-ISOMALTASE EXPRESSION BY EGF IN THE HUMAN COLON ADENOCARCINOMA CELLS CACO-2
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DOI：
10.1152/ajpcell.1991.261.6.c1173
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发表时间：
1991-12-01
影响因子：
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通讯作者：
QUARONI, A
中科院分区：
文献类型：
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作者：
CROSS, HS;QUARONI, A
为了探讨表皮生长因子（EGF）在肠上皮中的作用和机制，我们研究了EGF对Caco-2细胞增殖和分化的影响，Caco-2细胞是一种具有成人小肠上皮细胞特征的人结肠腺癌细胞系。在这些研究中使用了合成最少量转化生长因子-α（TGF-α）/表皮生长因子（EGF）样活性的Caco-2细胞克隆。在20-200 ng EGF/ml的存在下生长的细胞表现出增加的DNA合成和增殖;在200 ng EGF/ml下观察到形态学上分化不良的多层膜的形成。在所有浓度的测试EGF产生了显着和显着减少蔗糖酶活性，而其他刷状缘酶（氨肽酶N，碱性磷酸酶，二肽基肽酶IV）只受到轻微影响。EGF在两个不同的水平上影响蔗糖酶的表达。在20 ng/ml时，它主要影响内质网中的蔗糖酶-异麦芽糖酶加工和/或增加其降解。在200 ng EGF/ml时，观察到蔗糖酶-异麦芽糖酶mRNA水平和生物合成显著降低。这些结果表明，EGF对Caco-2细胞的增殖和分化具有重要的选择性作用，并可根据其浓度影响不同的细胞活性。
To investigate the role and mechanism of action of epidermal growth factor (EGF) in the intestinal epithelium, we have studied its influence on proliferation and differentiation of Caco-2 cells, a human colon adenocarcinoma cell line exhibiting several characteristics of adult small intestinal enterocytes. A clone of Caco-2 cells synthesizing minimal amounts of transforming growth factor-alpha (TGF-alpha)/epidermal growth factor (EGF)-like activity was used in these studies. Cells grown in the presence of 20-200 ng EGF/ml exhibited increased DNA synthesis and proliferation; formation of morphologically poorly differentiated multilayers was observed at 200 ng EGF/ml. At all concentrations tested EGF produced a significant and marked reduction in sucrase activity, whereas other brush-border enzymes (aminopeptidase N, alkaline phosphatase, dipeptidylpeptidase IV) were only marginally affected. EGF influenced sucrase expression at two different levels. At 20 ng/ml, it affected primarily sucrase-isomaltase processing in the endoplasmic reticulum and/or increased its degradation. At 200 ng EGF/ml, a significant and marked reduction in sucrase-isomaltase mRNA levels and biosynthesis was observed. These results demonstrated that EGF has important and selective effects on Caco-2 cell proliferation and differentiation and may affect different cellular activities depending on its concentration.