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The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis

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. A...

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Autores principales: Bossenmeyer-Pourié, Carine, Kannan, Rama, Ribieras, Stéphane, Wendling, Corinne, Stoll, Isabelle, Thim, Lars, Tomasetto, Catherine, Rio, Marie-Christine
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173421/
https://www.ncbi.nlm.nih.gov/pubmed/12034770
http://dx.doi.org/10.1083/jcb200108056
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author Bossenmeyer-Pourié, Carine
Kannan, Rama
Ribieras, Stéphane
Wendling, Corinne
Stoll, Isabelle
Thim, Lars
Tomasetto, Catherine
Rio, Marie-Christine
author_facet Bossenmeyer-Pourié, Carine
Kannan, Rama
Ribieras, Stéphane
Wendling, Corinne
Stoll, Isabelle
Thim, Lars
Tomasetto, Catherine
Rio, Marie-Christine
author_sort Bossenmeyer-Pourié, Carine
collection PubMed
description 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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spelling pubmed-21734212008-05-01 The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis Bossenmeyer-Pourié, Carine Kannan, Rama Ribieras, Stéphane Wendling, Corinne Stoll, Isabelle Thim, Lars Tomasetto, Catherine Rio, Marie-Christine J Cell Biol Article 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. The Rockefeller University Press 2002-05-28 /pmc/articles/PMC2173421/ /pubmed/12034770 http://dx.doi.org/10.1083/jcb200108056 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Bossenmeyer-Pourié, Carine
Kannan, Rama
Ribieras, Stéphane
Wendling, Corinne
Stoll, Isabelle
Thim, Lars
Tomasetto, Catherine
Rio, Marie-Christine
The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis
title The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis
title_full The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis
title_fullStr The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis
title_full_unstemmed The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis
title_short The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis
title_sort trefoil factor 1 participates in gastrointestinal cell differentiation by delaying g1-s phase transition and reducing apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173421/
https://www.ncbi.nlm.nih.gov/pubmed/12034770
http://dx.doi.org/10.1083/jcb200108056
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