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

Carine Bossenmeyer-Pourié1, Rama Kannan, Stéphane Ribieras

  • 1Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université Louis Pasteur, 67404 Illkirch Cedex, C.U. de Strasbourg, France.

The Journal of Cell Biology
|May 30, 2002
PubMed

Insights

Trefoil factor (TFF)1 acts as a gastric tumor suppressor by inhibiting cell proliferation and protecting against apoptosis. This dual role in cell regulation is crucial for understanding its function in gastrointestinal health.

Area of Science:

  • Gastroenterology and Molecular Biology
  • Oncology
  • Cellular Biology

Background:

  • Trefoil factor (TFF)1 is secreted by normal stomach mucosa and gastrointestinal cells.
  • TFF1 inactivation in mice leads to gastric tumors, classifying TFF1 as a gastric tumor suppressor gene.
  • Altered TFF1 expression, deletion, or mutations are common in human gastric carcinomas.

Purpose of the Study:

  • To investigate the cellular and molecular mechanisms of TFF1 signaling.
  • To elucidate the dual role of TFF1 in cell proliferation and apoptosis.

Main Methods:

  • Investigated TFF1 effects in IEC18, HCT116, and AGS gastrointestinal cells.
  • Utilized recombinant human TFF1 treatment and stable HCT116 cell transfection.
  • Analyzed cell cycle transition, apoptosis, and key molecular targets like caspase-9.

Main Results:

  • TFF1 delays the G1-S cell phase transition, reducing proliferation via increased cyclin-dependent kinase inhibitors and decreased E2F activity.
  • TFF1 protects cells from various apoptosis-inducing conditions.
  • TFF1 signaling targets the active form of caspase-9, inhibiting apoptosis.

Conclusions:

  • TFF1 exhibits a dual antiproliferative and antiapoptotic function.
  • These findings provide the first evidence for TFF1's opposing roles in cell regulation.
  • TFF1's functions align with those of tumor suppressor genes involved in cell differentiation.

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