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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)

Published on: December 19, 2019

Ei24-deficiency attenuates protein kinase Cα signaling and skin carcinogenesis in mice

Sushil Devkota1, Young Hoon Sung, Jung-Min Choi

  • 1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.

The International Journal of Biochemistry & Cell Biology
|July 10, 2012
PubMed

Insights

Etoposide-induced gene 24 (Ei24) deficiency reduces skin tumor growth and size in mice. Ei24 regulates the RINCK1-PKCα-EGFR pathway, suggesting a role in skin cancer development.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Etoposide-induced gene 24 (Ei24) is a p53 target gene with known tumor-suppressive functions.
  • Its role in in vivo tumorigenesis requires further investigation.

Purpose of the Study:

  • To evaluate the role of Ei24 in in vivo skin carcinogenesis.
  • To elucidate the molecular mechanisms underlying Ei24's function in cancer.

Main Methods:

  • Generation of Ei24-deficient mouse models (heterozygous and homozygous knockout).
  • DMBA/TPA-induced skin carcinogenesis model in mice.
  • Analysis of protein interactions and signaling pathways (RINCK1, PKCα, EGFR).
  • Bioinformatic analysis using the Oncomine database.

Main Results:

  • Ei24 homozygous knockout mice are embryonic lethal.
  • Ei24 heterozygous null mice exhibit reduced tumor number and size in DMBA/TPA-induced carcinogenesis.
  • Ei24 stabilizes PKCα by degrading RINCK1 and competes for PKCα binding.
  • Ei24 promotes PKCα membrane localization, enhancing EGFR transactivation.
  • Ei24 and EGFR are upregulated in human head and neck squamous cell carcinoma (HNSCC).

Conclusions:

  • Ei24 plays a significant role in regulating skin tumor development.
  • Ei24 acts as a regulator of the RINCK1-PKCα-EGFR signaling pathway.
  • These findings suggest Ei24's involvement in skin cancer pathogenesis and its potential as a therapeutic target.

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