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Updated: Jul 7, 2026

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
c-fos is required for malignant progression of skin tumors
E Saez1, S E Rutberg, E Mueller
1Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
The proto-oncogene c-fos is a major nuclear target for signal transduction pathways involved in the regulation of cell growth, differentiation, and transformation. Using the multistep skin carcinogenesis model, we have directly tested the ability of c-fos-deficient mice to develop cancer. Upon treatment with a tumor promoter, c-fos knockout mice carrying a v-H-ras transgene were able to develop benign tumors with similar kinetics and relative incidence as wild-type animals. However, c-fos-deficient papillomas quickly became very dry and hyperkeratinized, taking on an elongated, horny appearance. While wild-type papillomas eventually progressed into malignant tumors, c-fos-deficient tumors failed to undergo malignant conversion. Experiments in which v-H-ras-expressing keratinocytes were grafted onto nude mice suggest that c-fos-deficient cells have an intrinsic defect that hinders tumorigenesis. These results demonstrate that a member of the AP-1 family of transcription factors is required for the development of a malignant tumor.
Insights
The proto-oncogene c-FOS is essential for malignant tumor development. C-FOS-deficient mice developed benign tumors but failed to progress to malignancy, indicating its critical role in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The proto-oncogene c-FOS is a key nuclear target in cellular signaling pathways regulating cell growth, differentiation, and transformation.
- Understanding the role of c-FOS in carcinogenesis is crucial for developing targeted cancer therapies.
Purpose of the Study:
- To investigate the role of the c-FOS gene in the multistep process of skin carcinogenesis.
- To determine if c-FOS deficiency prevents the malignant conversion of benign tumors.
Main Methods:
- Utilized a multistep skin carcinogenesis model in c-FOS-deficient mice carrying a v-H-ras transgene.
- Compared tumor development and progression kinetics between c-FOS knockout and wild-type animals.
- Employed keratinocyte grafting experiments to assess cellular defects in tumorigenesis.
Main Results:
- c-FOS-deficient mice developed benign tumors with similar kinetics to wild-type mice.
- Papillomas in c-FOS-deficient mice exhibited hyperkeratinization and failed to progress to malignancy.
- Grafting experiments indicated an intrinsic cellular defect in tumorigenesis in c-FOS-deficient cells.
Conclusions:
- The transcription factor c-FOS, a member of the AP-1 family, is required for the malignant conversion of benign skin tumors.
- c-FOS plays a critical role in the progression of cancer, not initiation.
- Targeting c-FOS pathways may offer therapeutic strategies to prevent tumor malignancy.
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