Dysregulated ΔNp63α Inhibits Expression of Ink4a/arf, Blocks Senescence, and Promotes Malignant Conversion of Keratinocytes
2011

Oncogenic Activity of ΔNp63α in Skin Tumorigenesis

Sample size: 20 publication 10 minutes Evidence: high

Author Information

Author(s): Ha Linan, Ponnamperuma Roshini M., Jay Steven, Ricci M. Stacey, Weinberg Wendy C.

Primary Institution: Division of Monoclonal Antibodies, Center for Drug Evaluation and Research/Food and Drug Administration (CDER/FDA), Bethesda, Maryland, United States of America

Hypothesis

Elevated levels of ΔNp63α promote malignant conversion of keratinocytes by inhibiting senescence.

Conclusion

The study establishes that ΔNp63α has oncogenic activity and contributes to the malignant phenotype in human squamous cell carcinomas.

Supporting Evidence

  • Elevated levels of ΔNp63α promote long-term survival and block senescence in primary keratinocytes.
  • Lenti-ΔNp63α/v-rasHa keratinocytes form undifferentiated carcinomas, while lenti-GFP/v-rasHa develop benign papillomas.
  • ΔNp63α overexpression blocks the induction of p16ink4a/p19arf, key mediators of cell senescence.

Takeaway

This study shows that a protein called ΔNp63α helps skin cells survive and grow, which can lead to skin cancer.

Methodology

Lentiviruses were used to overexpress ΔNp63α in primary keratinocytes, and an in vivo grafting model was applied to assess tumorigenesis.

Participant Demographics

Primary keratinocytes isolated from the skin of 1-2 day-old C57B1/6NCr mice.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0021877

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