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The IGF-1/IGF-1R signaling axis in the skin: a new role for the dermis in aging-associated skin cancer
The appropriate response of human keratinocytes to UVB is dependent on the activation status of the IGF-1 receptor. Keratinocytes grown in conditions where the IGF-1 receptor is inactive, inappropriately replicate in the presence of UVB-induced DNA damage. In human skin epidermal keratinocytes do no...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837099/ https://www.ncbi.nlm.nih.gov/pubmed/19966862 http://dx.doi.org/10.1038/onc.2009.440 |
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author | Lewis, Davina A. Travers, Jeffrey B. Somani, Ally-Khan Spandau, Dan F |
author_facet | Lewis, Davina A. Travers, Jeffrey B. Somani, Ally-Khan Spandau, Dan F |
author_sort | Lewis, Davina A. |
collection | PubMed |
description | The appropriate response of human keratinocytes to UVB is dependent on the activation status of the IGF-1 receptor. Keratinocytes grown in conditions where the IGF-1 receptor is inactive, inappropriately replicate in the presence of UVB-induced DNA damage. In human skin epidermal keratinocytes do not express IGF-1, so the IGF-1 receptor on keratinocytes is activated by IGF-1 secreted from dermal fibroblasts. We now demonstrate that the IGF-1 produced by human fibroblasts is essential for the appropriate UVB response of keratinocytes. Furthermore, the expression of IGF-1 is silenced in senescent fibroblasts in vitro. Using quantitative RT-PCR and immunohistochemisty, we can demonstrate that IGF-1 expression is also silenced in geriatric dermis in vivo. The diminished IGF-1 expression in geriatric skin correlates with an inappropriate UVB response in geriatric volunteers. Finally, the appropriate UVB response is restored in geriatric skin in vivo via pretreatment with exogenous IGF-1. These studies provide further evidence for a role of the IGF-1R in suppressing UVB-induced carcinogenesis, suggest that fibroblasts play a critical role in maintaining appropriate activation of the keratinocyte IGF-1R, and imply that reduced expression of IGF-1 in geriatric skin could be an important component in the development of aging-related non-melanoma skin cancer. |
format | Text |
id | pubmed-2837099 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
record_format | MEDLINE/PubMed |
spelling | pubmed-28370992010-09-11 The IGF-1/IGF-1R signaling axis in the skin: a new role for the dermis in aging-associated skin cancer Lewis, Davina A. Travers, Jeffrey B. Somani, Ally-Khan Spandau, Dan F Oncogene Article The appropriate response of human keratinocytes to UVB is dependent on the activation status of the IGF-1 receptor. Keratinocytes grown in conditions where the IGF-1 receptor is inactive, inappropriately replicate in the presence of UVB-induced DNA damage. In human skin epidermal keratinocytes do not express IGF-1, so the IGF-1 receptor on keratinocytes is activated by IGF-1 secreted from dermal fibroblasts. We now demonstrate that the IGF-1 produced by human fibroblasts is essential for the appropriate UVB response of keratinocytes. Furthermore, the expression of IGF-1 is silenced in senescent fibroblasts in vitro. Using quantitative RT-PCR and immunohistochemisty, we can demonstrate that IGF-1 expression is also silenced in geriatric dermis in vivo. The diminished IGF-1 expression in geriatric skin correlates with an inappropriate UVB response in geriatric volunteers. Finally, the appropriate UVB response is restored in geriatric skin in vivo via pretreatment with exogenous IGF-1. These studies provide further evidence for a role of the IGF-1R in suppressing UVB-induced carcinogenesis, suggest that fibroblasts play a critical role in maintaining appropriate activation of the keratinocyte IGF-1R, and imply that reduced expression of IGF-1 in geriatric skin could be an important component in the development of aging-related non-melanoma skin cancer. 2009-12-07 2010-03-11 /pmc/articles/PMC2837099/ /pubmed/19966862 http://dx.doi.org/10.1038/onc.2009.440 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Lewis, Davina A. Travers, Jeffrey B. Somani, Ally-Khan Spandau, Dan F The IGF-1/IGF-1R signaling axis in the skin: a new role for the dermis in aging-associated skin cancer |
title | The IGF-1/IGF-1R signaling axis in the skin: a new role for the dermis in aging-associated skin cancer |
title_full | The IGF-1/IGF-1R signaling axis in the skin: a new role for the dermis in aging-associated skin cancer |
title_fullStr | The IGF-1/IGF-1R signaling axis in the skin: a new role for the dermis in aging-associated skin cancer |
title_full_unstemmed | The IGF-1/IGF-1R signaling axis in the skin: a new role for the dermis in aging-associated skin cancer |
title_short | The IGF-1/IGF-1R signaling axis in the skin: a new role for the dermis in aging-associated skin cancer |
title_sort | igf-1/igf-1r signaling axis in the skin: a new role for the dermis in aging-associated skin cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837099/ https://www.ncbi.nlm.nih.gov/pubmed/19966862 http://dx.doi.org/10.1038/onc.2009.440 |
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