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The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis

Victoria M Virador1, Rafael E Flores-Obando, Adam Berry

  • 1Laboratory of Cancer Biology and Genetics, Center for Cancer Research. National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA.

Molecular Carcinogenesis
|December 6, 2008
PubMed

Insights

This study investigated the role of the promyelocytic leukemia (PML) protein in skin cancer. Overexpressing PML in mice reduced tumor development, suggesting PML acts as a tumor suppressor in the skin.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • The PMLRARalpha fusion oncogene drives skin tumors via PML and RAR pathways.
  • The specific role of PML in skin tumor susceptibility requires further investigation.

Purpose of the Study:

  • To determine the contribution of PML to skin tumor susceptibility.
  • To investigate the function of PML in epidermal and hair follicle cells.

Main Methods:

  • Generated transgenic mice overexpressing human PML in epidermis and hair follicles.
  • Assessed skin phenotype, keratin 10 expression, and tumor development after DMBA/TPA treatment.
  • Analyzed cultured keratinocytes for senescence and gene expression.

Main Results:

  • PML overexpression increased keratin 10 expression and caused alopecia in aged mice.
  • Transgenic mice showed reduced papilloma multiplicity and delayed carcinoma conversion.
  • PML-expressing keratinocytes exhibited premature senescence and altered cell cycle regulator expression.

Conclusions:

  • PML plays a role in regulating keratinocyte growth and differentiation.
  • PML functions as a tumor suppressor in skin development and carcinogenesis.

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