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

Mathew M. Loesch, Ann E. Collier, David H. Southern, Rachel E. Ward, Sunil S. Tholpady, Davina A. Lewis, Jeffrey Travers, Dan Spandau

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalMolecular Oncology
DOIs
StateAccepted/In press - Mar 4 2016

Fingerprint

Somatomedin Receptors
Keratinocytes
DNA Damage
DNA Repair
Geriatrics
Insulin-Like Growth Factor I
Skin
Squamous Cell Carcinoma
Heterografts
Human Activities
Young Adult
Messenger RNA

Keywords

  • IGF-1R
  • Keratinocyte
  • NER
  • UVB
  • Xenograft

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Medicine

Cite this

Insulin-like growth factor-1 receptor regulates repair of ultraviolet B-induced DNA damage in human keratinocytes in vivo. / Loesch, Mathew M.; Collier, Ann E.; Southern, David H.; Ward, Rachel E.; Tholpady, Sunil S.; Lewis, Davina A.; Travers, Jeffrey; Spandau, Dan.

In: Molecular Oncology, 04.03.2016.

Research output: Contribution to journalArticle

Loesch, Mathew M. ; Collier, Ann E. ; Southern, David H. ; Ward, Rachel E. ; Tholpady, Sunil S. ; Lewis, Davina A. ; Travers, Jeffrey ; Spandau, Dan. / Insulin-like growth factor-1 receptor regulates repair of ultraviolet B-induced DNA damage in human keratinocytes in vivo. In: Molecular Oncology. 2016.
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