Differentiation of human colon adenocarcinoma cells alters the expression and intracellular localization of annexins A1, A2, and A5
Differentiation of human colon adenocarcinoma cells alters the expression and intracellular localization of annexins A1, A2, and A5
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DOI：
10.1002/jcb.20293
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发表时间：
2005-01-01
影响因子：
4
通讯作者：
Lizarbe, MA
中科院分区：
文献类型：
--
作者：
Guzmán-Aránguez, A;Olmo, N;Lizarbe, MA
丁酸通过调节多种基因的表达，诱导肠上皮细胞分化，改变细胞增殖。Annexins是一个普遍存在的蛋白质超家族，其特征是依赖钙离子与生物膜结合，参与多种生理过程，如膜转运、钙信号、细胞运动、增殖和分化等。因此，我们分析了膜联蛋白A1(AnxA1)、膜联蛋白A2(AnxA2)和膜联蛋白A5(AnxA5)在经丁酸盐处理或在无葡萄糖肌苷培养条件下分化的人结肠腺癌细胞中的水平和定位的变化。获得的分化表型增加了二肽基肽酶-IV(DPP-IV)的表达和碱性磷酸酶(ALP)的活性，这是两个众所周知的刷子边缘标记。丁酸盐诱导BCS-TC2、BCS-TC2.2、HT-29和Caco-2细胞分化和生长停滞，使AnxA1和AnxA5水平升高，而AnxA2水平下降，但Caco-2细胞除外。肌苷分化的细胞与自发分化的Caco-2细胞一样，呈现出所研究的三种膜联蛋白的增加。AnxA2的下调不是由于蛋白酶体的激活，而似乎与丁酸诱导的细胞增殖停滞有关；AnxA1和AnxA5的表达不依赖于生长状态。AnxA1和AnxA5主要存在于细胞质中，而AnxA2则定位于细胞与细胞接触的质膜下。丁酸盐诱导亚细胞定位的改变，转向囊泡相关的模式。人结肠腺癌细胞的分化与AnxA1、AnxA2和AnxA5的上调以及这些蛋白的亚细胞重新定位有关。未发现膜联蛋白水平与肿瘤发生之间的相关性。AnxA1的上调可能与丁酸盐在结肠炎性疾病中的抗炎作用有关。(C)2004年Wiley-Liss公司
Butyrate induces differentiation and alters cell proliferation in intestinal-epithelial cells by modulation of the expression of several genes. Annexins are a superfamily of ubiquitous proteins characterized by their calcium-dependent ability to bind to biological membranes; their involvement in several physiological processes, such as membrane trafficking, calcium signaling, cell motility, proliferation, and differentiation has been proposed. Thus, we have analyzed changes in annexin A1 (AnxA1), annexin A2 (AnxA2), and annexin A5 (AnxA5) levels and localization in human colon adenocarcinoma cells differentiated by butyrate treatment or by culture in glucose-free inosine-containing medium. The acquired differentiated phenotype increased dipeptidyl peptidase-IV (DPP-IV) expression and alkaline phosphatase (ALP) activity, two well known brush border markers. Butyrate induces cell differentiation and growth arrest in BCS-TC2, BCS-TC2.2, HT-29, and Caco-2 cells, increasing the levels of AnxA1 and AnxA5, whereas AnxA2 decreases except in Caco-2 cells. Inosine-differentiated cells present increased amounts of the three studied annexins, as occurs in spontaneously differentiated Caco-2 cells. AnxA2 down-regulation is not due to proteasome activation and seems to be related to the butyrate-induced cell proliferation arrest; AnxA1 and AnxA5 expression is growth-state independent. AnxA1 and AnxA5 are mainly found in the cytoplasm while AnxA2 is localized underneath the plasma membrane in cell-to-cell contacts. Butyrate induces changes in subcellular localization towards a vesicle-associated pattern. Human colon adenocarcinoma cell differentiation is associated with an up-regulation of AnxA1, AnxA2, and AnxA5 and with a subcellular relocation of these proteins. No correlation between annexin levels and tumorigenicity was found. Up-regulation of AnxA1 could contribute to the reported anti-inflammatory effects of butyrate in colon inflammatory diseases. (C) 2004 Wiley-Liss, Inc.