Loesch, Mathew M.Collier, Ann E.Southern, David H.Ward, Rachel E.Tholpady, Sunil S.Lewis, Davina A.Travers, Jeffrey B.Spandau, Dan F.2018-02-202018-02-202016-10Loesch, M. M., Collier, A. E., Southern, D. H., Ward, R. E., Tholpady, S. S., Lewis, D. A., … Spandau, D. F. (2016). Insulin‐like growth factor‐1 receptor regulates repair of ultraviolet B‐induced DNA damage in human keratinocytes in vivo. Molecular Oncology, 10(8), 1245–1254. https://doi.org/10.1016/j.molonc.2016.06.0021574-7891https://hdl.handle.net/1805/15255The 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., IGF‐1R is necessary for optimal repair of UVB‐induced DNA damage in keratinocytes.Novel separation technique allows study specifically in basal layer keratinocytes.IGF‐1R activation enhances the expression of nucleotide excision repair genes.en-USPublisher PolicyInsulingrowth factor‐1 receptorultraviolet BDNA damagekeratinocytes in vivoArticle