Activation of the ras/raf-1 signal transduction pathway in carcinoid tumor cells results in morphologic

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Rebecca S Sippel1, Herbert Chen

  • 1Department of Surgery, The University of Wisconsin Medical School, H4/750 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA.

Surgery
|December 20, 2002
PubMed
Abstract

Insights

Activating the ras/raf-1 pathway in gastrointestinal carcinoid cells induced significant morphologic changes, mimicking cellular differentiation. This suggests a novel mechanism for altering neuroendocrine tumor cell behavior.

Area of Science:

  • Cell biology
  • Molecular oncology
  • Signal transduction pathways

Background:

  • Neuroendocrine tumors (NETs) are a heterogeneous group of cancers.
  • Recent research suggests ras/raf-1 pathway activation may impact NET tumorigenesis.
  • The precise mechanism of ras/raf-1 pathway influence on NETs remains unclear.

Purpose of the Study:

  • To investigate the effects of ras/raf-1 signal transduction pathway activation on gastrointestinal carcinoid cells.
  • To determine if ras/raf-1 activation induces morphologic transdifferentiation in these cells.

Main Methods:

  • Stable transduction of pancreatic carcinoid (BON) cells with an estrogen-inducible raf-1 fusion protein.
  • Treatment of BON and engineered BON-raf cells with estradiol (E2) to activate raf-1.
  • Confirmation of extracellular signal-regulated kinase 1/2 phosphorylation via Western blot.
  • Evaluation of morphologic changes using light and electron microscopy.

Main Results:

  • Estradiol treatment successfully induced raf-1 activation and extracellular signal-regulated kinase 1/2 phosphorylation specifically in BON-raf cells.
  • BON-raf cells treated with estradiol exhibited dramatic morphologic alterations.
  • Microscopic analysis revealed that BON-raf cells became flatter with sharper cellular borders, resembling differentiated cells.

Conclusions:

  • Activation of the ras/raf-1 signal transduction pathway in vitro induces significant phenotypic changes in gastrointestinal carcinoid cells.
  • These observed changes closely mimic cellular differentiation.
  • The ras/raf-1 pathway represents a potential target for modulating NET cell behavior.

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