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Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
Transcription factors junB and c-jun are selectively up-regulated and functionally implicated in fibrosarcoma
E Bossy-Wetzel1, R Bravo, D Hanahan
1Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0534.
Genes & Development
|December 1, 1992
Summary
JunB and c-Jun proto-oncogenes drive tumor progression in bovine papillomavirus transgenic mice. These factors are crucial during intermediate fibromatosis stages, promoting cell shape changes and anchorage independence.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Bovine papillomavirus (BPV) induces skin tumors in transgenic mice.
- Tumor development progresses through mild fibromatosis, aggressive fibromatosis, and fibrosarcoma stages.
- Proto-oncogene expression patterns are critical in cancer progression.
Purpose of the Study:
- To investigate the role of junB, c-jun, junD, and fos proto-oncogenes in BPV-induced skin tumor development.
- To determine the functional significance of junB and c-jun in tumor progression.
Main Methods:
- Analysis of proto-oncogene expression in tumor tissue biopsies and cell lines.
- Assessment of AP-1 DNA-binding activity in fibrosarcoma cells.
- Gene transfection experiments to overexpress junB, c-jun, or junD in mild fibromatosis cells and normal fibroblasts.
Main Results:
- JunB and c-Jun were induced in aggressive fibromatosis and fibrosarcoma stages, unlike junD and fos.
- Fibrosarcoma cell lines exhibited elevated AP-1 DNA-binding activity.
- Overexpression of junB or c-jun in mild fibromatosis cells induced changes in cell shape and anchorage independence, while junD had no effect.
Conclusions:
- JunB and c-Jun act as progression factors in BPV-induced skin tumorigenesis.
- Their activity is essential during intermediate tumor development stages, following initial aberrant proliferation.
- These findings highlight specific jun genes as key mediators of tumor progression.
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