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The role of the transcription factor slug in the cutaneous response to ultraviolet radiation exposure

Newkirk, Kimberly Michelle
http://rave.ohiolink.edu/etdc/view?acc_num=osu1171998182

Abstract Details

2007, Doctor of Philosophy, Ohio State University, Veterinary Biosciences.
Slug is a member of the Snail family of zinc-finger transcription factors and has been implicated in epithelial-mesenchymal transformation (EMT). EMT occurs during embryonic development and wound healing, and contributes to the invasive behavior of neoplastic cells. To study the impact of Slug in normal skin, we compared patterns of gene expression in epidermis from Slug null and wild type mice. Functional classification of genes with altered expression was consistent with a role for Slug in keratinocyte development and differentiation, proliferation, apoptosis, adhesion, motility, angiogenesis and response to environmental stimuli. These categories have important implications for skin homeostasis, wound healing, and carcinogenesis. We then investigated the role of Slug in the response to ultraviolet radiation (UVR). Although the extent of direct UVR-induced DNA damage was similar in both genotypes, Slug knockout mice did not develop the sunburns that were observed in wild type mice. Additionally, Slug knockout mice had reduced dermal neutrophil infiltrates and epidermal hyperplasia post-UVR. The resistance of the knockout mice to the acute effects of UVR exposure could be explained by delayed and sometimes exaggerated cytokine expression in these mice following UVR exposure. These findings indicated an important role for Slug in the acute inflammatory and proliferative responses of the skin to UVR exposure. Since chronic inflammation is strongly linked to carcinogenesis, we evaluated the role of Slug in the chronic UVR exposure and UVR-induced tumor formation. As compared to the wild type mice, Slug null mice had less cutaneous inflammation, less epidermal proliferation, a lower tumor burden, and a tendency to develop fewer aggressive spindle cell tumors – which arise from EMT within squamous cell carcinomas. Furthermore, we identified decreased vimentin and increased E-cadherin expression in these tumors suggesting impaired EMT in the Slug knockout mice, and therefore the potential for reduced invasive or metastatic capabilities. This study confirmed a role for Slug in skin carcinogenesis and EMT, but demonstrated that Slug is not required for the development or progression of UVR-induced skin tumors Overall, our studies have demonstrated unexpected roles for Slug in epidermal homeostasis, the cutaneous inflammatory response and in skin carcinogenesis.
Donna Kusewitt (Advisor)
199 p.
Biology, Veterinary Science
Slug; mouse; UVR; carcinogenesis; skin

Recommended Citations

Citations

  • Newkirk, K. M. (2007). The role of the transcription factor slug in the cutaneous response to ultraviolet radiation exposure [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1171998182

    APA Style (7th edition)

  • Newkirk, Kimberly. The role of the transcription factor slug in the cutaneous response to ultraviolet radiation exposure. 2007. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1171998182.

    MLA Style (8th edition)

  • Newkirk, Kimberly. "The role of the transcription factor slug in the cutaneous response to ultraviolet radiation exposure." Doctoral dissertation, Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1171998182

    Chicago Manual of Style (17th edition)

osu1171998182
1,167
© 2007, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.
Release 3.2.12