Oncogenic K-Ras and basic fibroblast growth factor prevent Fas-mediated apoptosis in fibroblasts through activation

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Updated: Jul 31, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

H Kazama1, S Yonehara

  • 1Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.

The Journal of Cell Biology
|February 9, 2000
PubMed

Insights

Proto-oncogene c-K-ras inhibits Fas-mediated apoptosis by activating the MAPK pathway. This Ras-MAPK signaling protects cells from apoptosis, potentially contributing to cancer development.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Fas-mediated apoptosis is a critical cellular process.
  • Proto-oncogenes, like c-K-ras, play roles in cell growth and survival.
  • Understanding the regulation of apoptosis is crucial for cancer research.

Purpose of the Study:

  • To identify genes that inhibit Fas-mediated apoptosis.
  • To elucidate the role of c-K-ras and its downstream pathways in apoptosis regulation.
  • To investigate the link between Ras signaling, MAPK activation, and apoptosis in oncogenesis.

Main Methods:

  • Expression cloning using Fas-transgenic Balb3T3 cells.
  • Transient expression of K-Ras mutants and downstream pathway components (Raf, PI-3 kinase, RalGDS).
  • Analysis of caspase activation, MAPK pathway activation, and cell apoptosis.

Main Results:

  • Oncogenic K-Ras (RasV12) inhibited Fas-mediated apoptosis, while dominant-inhibitory K-Ras (RasN17) enhanced it.
  • Activation of the MAPK pathway, specifically through Raf and MAPKK, inhibited apoptosis.
  • MKP-1, a MAPK phosphatase, reversed the anti-apoptotic effects, and bFGF-induced Ras activation protected cells via MAPK.

Conclusions:

  • Ras activation of the MAPK pathway inhibits Fas-mediated apoptosis in Balb3T3 cells.
  • This anti-apoptotic mechanism mediated by Ras and MAPK may contribute to cellular transformation and oncogenesis.
  • The findings highlight a novel role for Ras-MAPK signaling in preventing programmed cell death, relevant to cancer biology.

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