Heregulin β-1 induces loss of cell-cell contact and enhances expression of MUC1 at the cell surface in HCC2998 and MKN45-1 cells.
Heregulin β-1 induces loss of cell-cell contact and enhances expression of MUC1 at the cell surface in HCC2998 and MKN45-1 cells.
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DOI：
10.1371/journal.pone.0029599
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Fukui Y
中科院分区：
文献类型：
--
作者：
Okoshi R;Shu CL;Ihara S;Fukui Y
本文研究了HcC2998和MKN45-1细胞在HERG刺激下的信号转导和细胞反应。这两种细胞被用作研究印戒细胞癌形成的模型系统。印戒环癌是一种低分化腺癌。HRG刺激导致细胞变圆，对HRG作出反应。在刺激后，对照细胞中存在的粘连连接被破坏，细胞与细胞之间的相互作用消失。抑制磷脂酰肌醇(PI)-3激酶或p38-MAP激酶可阻断该反应，表明该反应需要PI-3-P38-MAP激酶途径。抑制p38MAPK通路可立即恢复细胞间的相互作用。这一结果表明，黏附分子的信号转导受到生长因子信号的严格调控。也观察到MUC1在细胞表面的表达，并发现只有在HRG刺激后才有表达。MUC1的总量保持不变，表明这一数量不是由于基因表达的诱导，而是MUC1从内膜到质膜的转位。该反应不依赖于细胞粘附素途径，但依赖于PI-3激酶的活性。除了这些反应外，HRG还刺激HCC2998和MKN45-1细胞的生长，这取决于ERK途径，因为MEK抑制剂取消了这一作用。因此，HRG通过不同的途径诱导HCC2998和MKN45-1细胞发生不同的反应。这些反应都与肿瘤的特性有关，这意味着HRG信号可以促进肿瘤的形成。
Signal transduction and cell responses after stimulation with heregulin β-1 (HRG) are examined in HCC2998 and MKN45-1 cells, which have been used for a model system to study the formation of signet ring carcinomas, one of poorly differentiated adenocarcinomas. HRG stimulation causes rounding of the cells, responding to HRG. The adherens junction, which is present in the control cells, is disrupted and cell-cell interaction is lost after stimulation. Inhibition of phosphatidylinositol (PI)-3 kinase or p38 MAP kinase blocked this reaction, which indicates that the PI-3 kinase-p38 MAP kinase pathway is required for this reaction. Inhibition of the p38 MAP kinase pathway resulted in immediate restoration of cell-cell interaction. This result indicates that signaling for adherent molecules is strictly regulated by growth factor signaling. Expression of MUC1 at the cell surface is also observed and found to be expressed only after HRG stimulation. The total amount of MUC1 remains unchanged, suggesting that this amount is not due to induction of gene expression but to translocation of MUC1 from the inner membrane to the plasma membrane. This reaction is independent of the cytohesin pathway but dependent on PI-3 kinase activity. In addition to these reactions, HRG stimulates cell growth of both HCC2998 and MKN45-1 cells, depending on the ERK pathway given that the MEK inhibitor abolishes this effect. Therefore, HRG induces various reactions in HCC2998 and MKN45-1 cells by different pathways. These reactions are all related to characteristics of tumors, which implicates that HRG signaling can contribute to the formation of tumors.
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影响因子：
8
作者：
Kobayashi, M;Iwamatsu, A;Fukui, Y
通讯作者：
Fukui, Y
DOI：
10.1073/pnas.82.19.6497
发表时间：
1985-01-01
影响因子：
11.1
作者：
SEMBA, K;KAMATA, N;YAMAMOTO, T
通讯作者：
YAMAMOTO, T
影响因子：
7.5
作者：
Bublil, Erez M.;Yarden, Yosef
通讯作者：
Yarden, Yosef
DOI：
10.1073/pnas.96.9.4874
发表时间：
1999-04-27
影响因子：
11.1
作者：
Kobayashi, M;Nagata, S;Fukui, Y
通讯作者：
Fukui, Y
DOI：
10.1007/bf02471470
发表时间：
1988-07-01
期刊：
JAPANESE JOURNAL OF SURGERY
影响因子：
--
作者：
AKIYAMA, S;AMO, H;TAKAGI, H
通讯作者：
TAKAGI, H