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ERBB2 Is Essential for the Growth of Chemically Induced Skin Tumors in Mice

Maik Dahlhoff1, Sukalp Muzumdar2, Matthias Schäfer2

  • 1Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany.

The Journal of Investigative Dermatology
|December 10, 2016
PubMed

Insights

The study found that ERBB2 (ErbB2) is not essential for normal skin development but is crucial for wound healing and skin cancer progression in mice. Targeting ERBB2 may help inhibit nonmelanoma skin cancer.

Area of Science:

  • Dermatology
  • Oncology
  • Molecular Biology

Background:

  • Epidermal growth factor receptor (EGFR) is known to play roles in skin carcinogenesis and wound healing.
  • The function of the related receptor ERBB2 in skin tissues is less understood.
  • Investigating ERBB2's role is important for understanding skin homeostasis and disease.

Purpose of the Study:

  • To investigate the role of ERBB2 in mouse skin homeostasis, wound healing, and chemical carcinogenesis.
  • To determine if ERBB2 is essential for normal epidermal development and function.
  • To explore ERBB2 as a potential therapeutic target for skin cancers.

Main Methods:

  • Used keratin 5-directed, cre recombinase-mediated targeting to create Erbb2-deficient mice (Erbb2del) specifically in keratinocytes.
  • Assessed skin abnormalities, wound healing responses, and tumor development following a chemical carcinogenesis protocol (7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate).
  • Analyzed keratinocyte proliferation rates in both wound healing and chemically induced tumor models.

Main Results:

  • Erbb2del mice showed no spontaneous skin abnormalities, indicating ERBB2 is dispensable for epidermal homeostasis.
  • Wound healing was impaired in Erbb2del mice, with reduced epithelial thickness and keratinocyte proliferation.
  • Erbb2del mice exhibited delayed papilloma formation and reduced tumor burden during chemical carcinogenesis, with decreased tumor cell proliferation.
  • Loss of ERBB2 also reduced keratinocyte proliferation following 12-O-tetradecanoylphorbol-13-acetate application.

Conclusions:

  • ERBB2 is not required for the development and maintenance of the epidermis and its appendages.
  • ERBB2 plays a significant pro-proliferative role, essential for normal skin wound healing.
  • ERBB2 is required for the progression of chemically induced skin tumors in mice, suggesting it as a potential therapeutic target for nonmelanoma skin cancer.

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