Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Molecular oncology, 2016-10, Vol.10 (8), p.1245-1254

Ort / Verlag

United States: Elsevier B.V

Erscheinungsjahr

2016

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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. •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.