Insulin-like growth factor-1 receptor regulates repair of ultraviolet B-induced DNA damage in human keratinocytes in vivo

Mol Oncol. 2016 Oct;10(8):1245-54. doi: 10.1016/j.molonc.2016.06.002. Epub 2016 Jun 16.


The activation status of the insulin-like growth factor-1 receptor (IGF-1R) regulates the cellular response of keratinocytes to ultraviolet B (UVB) exposure, both in vitro and in vivo. Geriatric skin is deficient in IGF-1 expression resulting in an aberrant IGF-1R-dependent UVB response which contributes to the development of aging-associated squamous cell carcinoma. Furthermore, our lab and others have reported that geriatric keratinocytes repair UVB-induced DNA damage less efficiently than young adult keratinocytes. Here, we show that IGF-1R activation influences DNA damage repair in UVB-irradiated keratinocytes. Specifically, in the absence of IGF-1R activation, the rate of DNA damage repair following UVB-irradiation was significantly slowed (using immortalized human keratinocytes) or inhibited (using primary human keratinocytes). Furthermore, inhibition of IGF-1R activity in human skin, using either ex vivo explant cultures or in vivo xenograft models, suppressed DNA damage repair. Primary keratinocytes with an inactivated IGF-1R also exhibited lower steady-state levels of nucleotide excision repair mRNAs. These results suggest that deficient UVB-induced DNA repair in geriatric keratinocytes is due in part to silenced IGF-1R activation in geriatric skin and provide a mechanism for how the IGF-1 pathway plays a role in the initiation of squamous cell carcinoma in geriatric patients.

Keywords: IGF-1R; Keratinocyte; NER; UVB; Xenograft.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA Damage*
  • DNA Repair / genetics
  • DNA Repair / radiation effects*
  • Gene Expression Regulation / radiation effects
  • Humans
  • Keratinocytes / metabolism*
  • Keratinocytes / radiation effects*
  • Kinetics
  • Male
  • Mice, Inbred NOD
  • Mice, SCID
  • Receptor, IGF Type 1 / metabolism*
  • Telomerase / metabolism
  • Ultraviolet Rays*
  • Xenograft Model Antitumor Assays


  • Receptor, IGF Type 1
  • Telomerase