Upregulation of fibroblast growth factors and their receptors during multi-stage epidermal carcinogenesis in K14-HPV16 transgenic mice

Oncogene. 1996 Nov 7;13(9):1847-57.


Upregulation of acidic and basic fibroblast growth factors (FGF-1 and -2), and their cognate receptors FGFR-1 and -2, has been demonstrated in a variety of epithelial malignancies. However, the patterns of FGF/FGFR expression at specific stages of epithelial carcinogenesis have not been extensively characterized. In this report, the levels of FGF-1, FGF-2, FGF-7 mRNA and their receptors FGFR-1 and FGFR-2, were investigated during epidermal carcinogenesis in transgenic mice expressing the early region of the 'high risk' papillomavirus type 16 (HPV16) under control of the human keratin-14 enhancer/promoter (K14-HPV16 transgenic mice). FGF-1 was first upregulated in dysplasias, while FGF-2 was constitutively expressed in non-transgenic, neoplastic, and malignant keratinocytes throughout carcinogenesis. Expression of FGF-7 was undetectable in non-transgenic epidermis, and remained at threshold levels at all stages of progression. In well differentiated squamous cancers, FGFR-1 was upregulated and co-localized with angiogenic capillaries in the dermis underlying dysplastic lesions and within papillary fronds of invasive cancers. In contrast, FGFR-1 was upregulated specifically within the malignant squamous cells of moderate-poorly differentiated squamous cancers. The expression of FGFR-2 was essentially constitutive in both non-transgenic and neoplastic epidermis. Collectively the data suggest that the FGF/FGFR signaling pathways may potentially contribute to several facets of multi-stage epithelial carcinogenesis, including auto- or paracrine growth stimulation, upregulation of angiogenesis, and stromal remodeling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 2 / biosynthesis
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors / biosynthesis*
  • Fibroblast Growth Factors / genetics
  • Growth Substances / biosynthesis
  • Growth Substances / genetics
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Mice
  • Mice, Transgenic
  • Neoplasm Metastasis
  • Neoplasms, Squamous Cell / genetics
  • Neoplasms, Squamous Cell / metabolism
  • Neoplasms, Squamous Cell / pathology
  • Papillomaviridae / genetics*
  • RNA, Messenger / biosynthesis
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor / biosynthesis
  • Receptors, Fibroblast Growth Factor / genetics
  • Skin / metabolism
  • Skin / pathology
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Up-Regulation / genetics*


  • Fgf7 protein, mouse
  • Fibroblast Growth Factor 10
  • Growth Substances
  • RNA, Messenger
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors
  • Fgfr1 protein, mouse
  • Fgfr2 protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2