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The role of fibroblast growth factor receptor 2b in skin homeostasis and cancer development

Richard Grose1, Vera Fantl, Sabine Werner

  • 1Centre for Tumour Biology, Institute of Cancer, Bart's & The London, Queen Mary's School of Medicine & Dentistry, London, UK. r.p.grose@qmul.ac.uk

The EMBO Journal
|February 17, 2007
PubMed

Insights

Fibroblast growth factor receptor 2b (Fgfr2b) deletion in skin cells causes hair and gland abnormalities. Loss of Fgfr2b also increases skin cancer susceptibility, revealing its tumor suppressive role.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Developmental Biology

Background:

  • The epithelial fibroblast growth factor receptor 2b (Fgfr2b) is critical for embryonic development, with null mutations causing embryonic lethality.
  • Its role in post-natal skin development and homeostasis remains largely unexplored.

Purpose of the Study:

  • To investigate the function of Fgfr2b in adult skin development and homeostasis.
  • To determine the role of Fgfr2b in skin carcinogenesis and inflammatory responses.

Main Methods:

  • Utilized Cre-Lox transgenic technology to specifically delete Fgfr2b in keratin 5-expressing epidermal cells.
  • Analyzed skin phenotype, tumor development after chemical carcinogen exposure, and gene expression profiles in mutant mice.

Main Results:

  • Mice lacking epidermal Fgfr2b survived to adulthood but exhibited hair and sebaceous gland abnormalities, epidermal hyperthickening, and spontaneous papilloma formation.
  • Mutant mice showed increased sensitivity to chemical carcinogens, developing papillomas and squamous cell carcinomas, alongside heightened skin inflammation with altered immune cell populations.
  • Gene expression analysis revealed increased interleukin 18 and decreased Serpin a3b in mutant skin.

Conclusions:

  • Fgfr2b plays a crucial role in post-natal skin development, homeostasis, and suppresses tumor formation in the epidermis.
  • This study provides the first evidence of a tyrosine kinase receptor functioning as a tumor suppressor in the skin.

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