The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis.
The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis.
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DOI：
10.1083/jcb200108056
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发表时间：
2002-05-27
期刊：
影响因子：
--
通讯作者：
Rio MC
中科院分区：
文献类型：
--
作者：
Bossenmeyer-Pourié C;Kannan R;Ribieras S;Wendling C;Stoll I;Thim L;Tomasetto C;Rio MC
三叶因子（TFF）1由正常胃黏膜和损伤组织的胃肠道细胞合成和分泌。小鼠TFF1失活与完全渗透的幽门癌表型之间的联系促使TFF1被归类为胃肿瘤抑制基因。因此，在人胃癌中经常观察到TFF1基因的表达改变、缺失和/或突变。本研究旨在探讨TFF1信号传导的细胞和分子机制的本质。用重组人TFF1处理IEC18、HCT116和AGS胃肠道细胞，以及稳定转染合成本构型或强力霉素诱导的人TFF1的HCT116细胞，研究TFF1的作用。我们观察到TFF1触发两种类型的细胞反应。一方面，TFF1通过延缓G1-S细胞的相变来降低细胞增殖。这是由于tff1介导的INK4和CIP亚家族细胞周期蛋白依赖性激酶抑制剂水平的增加，导致E2F转录活性降低。另一方面，TFF1保护细胞免受化学、无锚定或bad诱导的细胞凋亡。在这个过程中，TFF1信号靶向caspase-9的活性形式。总之，这些结果提供了TFF1具有双重抗增殖和抗凋亡作用的第一个证据。在参与细胞分化的肿瘤抑制基因中也有类似的自相矛盾的功能，其功能与TFF1一致。
Trefoil factor (TFF)1 is synthesized and secreted by the normal stomach mucosa and by the gastrointestinal cells of injured tissues. The link between mouse TFF1 inactivation and the fully penetrant antropyloric tumor phenotype prompted the classification of TFF1 as a gastric tumor suppressor gene. Accordingly, altered expression, deletion, and/or mutations of the TFF1 gene are frequently observed in human gastric carcinomas. The present study was undertaken to address the nature of the cellular and molecular mechanisms targeted by TFF1 signalling. TFF1 effects were investigated in IEC18, HCT116, and AGS gastrointestinal cells treated with recombinant human TFF1, and in stably transfected HCT116 cells synthesizing constitutive or doxycycline-induced human TFF1. We observed that TFF1 triggers two types of cellular responses. On one hand, TFF1 lowers cell proliferation by delaying G1-S cell phase transition. This results from a TFF1-mediated increase in the levels of cyclin-dependent kinase inhibitors of both the INK4 and CIP subfamilies, leading to lower E2F transcriptional activity. On the other hand, TFF1 protects cells from chemical-, anchorage-free–, or Bad-induced apoptosis. In this process, TFF1 signalling targets the active form of caspase-9. Together, these results provide the first evidence of a dual antiproliferative and antiapoptotic role for TFF1. Similar paradoxical functions have been reported for tumor suppressor genes involved in cell differentiation, a function consistent with TFF1.
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影响因子：
4.8
作者：
Datta, R;Oki, E;Kufe, D
通讯作者：
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影响因子：
1.6
作者：
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作者：
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DOI：
10.1152/ajpcell.1998.275.5.c1193
发表时间：
1998-11-01
影响因子：
5.5
作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
VOGELSTEIN, B