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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

Elevated basal reactive oxygen species and phospho-Akt in murine keratinocytes resistant to ultraviolet B-induced

Brent D Butts1, Kevin A Kwei, G Tim Bowden

  • 1Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, Arizona 85724, USA.

Molecular Carcinogenesis
|July 29, 2003
PubMed

Insights

Malignant cells resist apoptosis via elevated reactive oxygen species (ROS) that activate Akt kinase. This study shows ROS-induced Akt phosphorylation increases resistance to UVB-induced apoptosis, a key step in skin cancer progression.

Area of Science:

  • Cell Biology
  • Dermatology
  • Oncology

Background:

  • Apoptosis resistance is crucial for skin carcinogenesis.
  • Akt kinase regulates apoptosis and is activated by reactive oxygen species (ROS).
  • Malignant keratinocyte variants (6M90, 6R90) exhibit elevated ROS due to reduced catalase activity, conferring a growth advantage.

Purpose of the Study:

  • To investigate the role of chronically increased ROS in apoptosis resistance during skin carcinogenesis.
  • To determine the mechanism by which elevated ROS contributes to apoptosis resistance.
  • To explore the link between ROS, Akt phosphorylation, and resistance to ultraviolet (UV) B-induced apoptosis.

Main Methods:

  • Comparison of apoptosis resistance in malignant keratinocyte variants and parental cells.
  • Assessment of Akt phosphorylation levels in relation to ROS.
  • Modulation of ROS levels via catalase overexpression and antioxidant treatment.
  • Treatment of normal keratinocytes with hydrogen peroxide to induce ROS.

Main Results:

  • Chronically elevated ROS in malignant variants increased resistance to UVB-induced apoptosis.
  • This resistance correlated with basal increases in Akt phosphorylation.
  • Modulating ROS levels altered Akt phosphorylation and apoptosis resistance.
  • Hydrogen peroxide treatment increased Akt phosphorylation and apoptosis resistance in normal cells.

Conclusions:

  • Chronically elevated ROS in tumors promotes a malignant phenotype by maintaining Akt phosphorylation.
  • This sustained Akt activation leads to increased apoptosis resistance, facilitating cancer development.
  • Targeting ROS or Akt pathways may offer therapeutic strategies for skin cancer.

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