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Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin
10:51

Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin

Published on: July 14, 2017

Inhibition of beta-TrCP function potentiates UVB-induced apoptosis in hTERT-immortalized normal human keratinocytes

Neehar Bhatia1, Tara A Demmer, Vladimir S Spiegelman

  • 1Department of Dermatology and Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Photochemistry and Photobiology
|January 23, 2008
PubMed

Insights

UV radiation causes DNA damage, potentially leading to skin cancer. Inhibiting beta-TrCP2 enhances UVB-induced apoptosis in skin cells, independent of p53 and NF-kappaB pathways.

Area of Science:

  • Molecular Biology
  • Dermatology
  • Cancer Research

Background:

  • Chronic UV radiation exposure causes DNA damage and mutations, increasing skin cancer risk.
  • The ubiquitin proteasome pathway, particularly SCFbetaTrCP E3 ligases, degrades key proteins in tumorigenesis.
  • beta-TrCP1/2 activity is elevated in activated signaling pathways involved in tumorigenesis.

Purpose of the Study:

  • To establish and characterize immortalized human keratinocytes (STINKs) for studying UVB responses.
  • To analyze the response of STINKs to UVB radiation, focusing on p53 and NF-kappaB markers.
  • To investigate the role of beta-TrCP2 in UVB-induced apoptosis.

Main Methods:

  • Established immortalized human neonatal foreskin keratinocytes (STINKs) using hTERT.
  • Analyzed STINKs' response to UVB radiation, assessing p53 and NF-kappaB.
  • Induced dominant-negative beta-TrCP2 (beta-TrCP2DeltaN) to inhibit beta-TrCP2 function.

Main Results:

  • STINKs maintained keratinocyte characteristics, including keratin expression and calcium susceptibility.
  • UVB radiation induced characteristic responses in STINKs.
  • Inhibition of beta-TrCP2 function significantly enhanced UVB-induced apoptosis.
  • Enhanced apoptosis was independent of p53 and NF-kappaB pathways.

Conclusions:

  • STINKs serve as a valuable model for studying skin responses to UVB radiation.
  • Beta-TrCP2 plays a significant role in regulating UVB-induced apoptosis in keratinocytes.
  • Targeting beta-TrCP2 may offer a novel therapeutic strategy for skin cancer prevention or treatment.

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