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.

Cell
|September 8, 1995
PubMed

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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