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[Inheritable phenotypic normalization of rodent cells transformed by simian adenovirus SA7 E1 oncogenes by
N I Grineva1, T V Borovkova, N V Sats
1Hematology Research Center, Russian Academy of Medical Sciences, Moscow 125167 Russia.
Abstract:
G11 mouse cells and SH2 rat cells transformed with simian adenovirus SA7 DNA showed inheritable oncogen-specific phenotypic normalization when treated with sense and antisense oligonucleotides complementary to long RNA sequences, plus or minus strands of the integrated adenovirus oncogenes E1A and E1B. Transitory treatment of the cells with the oligonucleotides in the absence of serum was shown to cause the appearance of normalized cell lines with fibroblastlike morphology, slower cell proliferation, and lack of ability to form colonies in soft agar. Proliferative activity and adhesion of the normalized cells that established cell lines were found to depend on the concentration of growth factors in the cultural medium. In some of the cell lines, an inhibition of transcription of the E1 oncogenes was observed. The normalization also produced cells that divided 2 - 5 times and died and cells that reverted to a transformed phenotype in 2 - 10 days. The latter appeared predominantly upon the action of the antisense oligonucleotides.
Insights
Oncogene-specific phenotypic normalization in cancer cells was achieved using sense and antisense oligonucleotides targeting adenovirus oncogenes. This approach offers a novel strategy for cancer research and potential therapeutic development.
Area of Science:
- Molecular Biology
- Oncology
- Gene Therapy
Context:
- Simian adenovirus SA7 DNA-induced transformation of G11 mouse and SH2 rat cells.
- Integrated adenovirus oncogenes E1A and E1B drive tumor formation.
Purpose:
- To investigate the potential of sense and antisense oligonucleotides for phenotypic normalization of oncogene-transformed cells.
- To evaluate the stability and characteristics of normalized cell lines.
Summary:
- Treatment with oligonucleotides complementary to adenovirus oncogenes E1A and E1B induced inheritable phenotypic normalization in transformed cells.
- Normalized cell lines exhibited fibroblast-like morphology, reduced proliferation, and loss of anchorage-independent growth.
- Normalization effects were dependent on growth factor concentrations, with some lines showing E1 oncogene transcription inhibition.
Impact:
- Demonstrates a method for reversing oncogenic phenotypes using targeted oligonucleotide therapy.
- Highlights the role of adenovirus E1 oncogenes in maintaining cellular transformation.
- Suggests potential for oligonucleotide-based strategies in cancer treatment and research.