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Revertants of v-fos-transformed fibroblasts have mutations in cellular genes essential for transformation by other oncogenes

  • 0Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Quebec, Canada.
Cell +

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November 6, 1987

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November 6, 1987

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Summary

This summary is machine-generated.

Researchers identified cellular genes crucial for oncogene-induced cell transformation. Mutations in these genes, identified in FBJ murine sarcoma virus (v-fos) revertants, confer resistance to certain oncogenes, suggesting common transformation pathways.

Area Of Science

  • Molecular Biology
  • Cell Biology
  • Oncology

Background

  • FBJ murine sarcoma virus (v-fos) transformation of rat-1 fibroblasts leads to altered cellular morphology.
  • Identifying the genetic basis of transformation resistance is key to understanding oncogenic pathways.

Purpose Of The Study

  • To isolate and characterize morphologic revertants of v-fos-transformed fibroblasts.
  • To investigate the genetic mutations underlying resistance to oncogene-induced transformation.
  • To explore common biochemical pathways involved in cellular transformation.

Main Methods

  • Utilized a novel selection procedure based on rhodamine 123 retention in mitochondria.
  • Isolated and classified morphologic revertants into Class I (cellular gene mutations) and Class II (nonfunctional v-fos provirus).
  • Performed somatic-cell hybridization studies to assess phenotype dominance.
  • Tested retransformation susceptibility using various oncogenes (v-gag-fos-fox, v-Ha-ras, v-abl, v-mos, trk, polyoma virus middle T antigen).

Main Results

  • Two classes of revertants were identified: Class I with cellular gene mutations and Class II with a nonfunctional v-fos provirus.
  • The revertant phenotype was found to be recessive to the transformed phenotype.
  • Class I revertants exhibited resistance to retransformation by several oncogenes but remained susceptible to others, including the trk oncogene and polyoma virus middle T antigen.
  • These findings indicate mutations in specific cellular genes can block transformation mediated by a subset of oncogenes.

Conclusions

  • Class I revertants possess mutations in cellular genes essential for transformation by specific oncogenes.
  • The data support the existence of common biochemical pathways utilized by different oncogenes for cellular transformation.
  • This study provides insights into the genetic regulation of cell transformation and potential therapeutic targets.

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