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Reversal of transformed phenotypes by antisense fos

M O Bradley1, S Manam, A R Kraynak

  • 1Genetic MediSyn Corporation, Rockville, Maryland 20850.

Annals of the New York Academy of Sciences
|October 28, 1992
PubMed

Insights

Antisense DNA targeting c-fos translation reversed the oncogenic phenotype in H-ras cells. This approach significantly inhibited tumor growth, suggesting potential therapeutic benefits for cancers driven by oncogenes.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Oncology

Background:

  • Antisense DNA technology offers a novel therapeutic strategy.
  • Targeting oncogenic pathways, such as the fos pathway, is crucial for cancer treatment.
  • Ras-transformed cells exhibit an aggressive oncogenic phenotype.

Purpose of the Study:

  • To investigate the therapeutic potential of antisense DNA in down-regulating the oncogenic phenotype of H-ras transformed cells.
  • To determine if antisense-mediated down-regulation of c-fos translation could reverse tumorigenic characteristics.

Main Methods:

  • Transfection of H-ras cells with an 84-base antisense-fos sequence under a dexamethasone-inducible promoter.
  • Assessment of cell morphology, growth in low serum, soft agar colony formation, and tumor growth in nude mice.
  • Quantification of c-fos protein levels via immunofluorescence and analysis of ras expression.

Main Results:

  • Antisense-fos clones exhibited density-dependent growth, flat morphology, and quiescence in low serum.
  • Soft agar growth was inhibited to 1% of control values, and tumor growth in nude mice was dramatically reduced.
  • Antisense-fos significantly reduced c-fos protein levels without affecting ras expression.

Conclusions:

  • Down-regulation of c-fos translation using antisense DNA can reverse the oncogenic phenotype in ras-transformed cells.
  • Antisense therapeutic compounds hold promise for treating cancers driven by ras or other oncogenes.
  • Targeting signal transduction pathways offers a viable strategy for developing novel anti-cancer therapies.

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