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Alterations in Endogenous Retinoids with Acute UVB Exposure and in the Progression of Cutaneous Squamous Cell Carcinoma

Gressel, Katherine Lynne

Abstract Details

2015, Master of Science, Ohio State University, Human Ecology: Human Nutrition.
Exposure to UVB light is the largest risk factor for the development of cutaneous squamous cell carcinoma (cSCC), one of the most common cancers in the United States. UVB exposure causes many changes to occur in the skin such as epidermal thickening, hyperproliferation, and alterations to epidermal differentiation. Retinoids regulate the differentiation and proliferation of the epidermis. The purpose of this study is to examine how the expression of retinoid metabolism proteins in the epidermis is altered with acute UVB exposure and in the progression of cSCC. There is limited knowledge of how UVB exposure may affect this pathway; our results will allow us to gain a more complete understanding of changes in the entire retinoid metabolism pathway. We examined the expression of key retinoic acid metabolism proteins in the epidermis and hair follicle remnants 48 hours after UVB exposure in SKH-1 mice using immunohistochemistry. UVB exposure increased the expression of retinoid synthesis, degradation, and binding proteins. These changes in expression suggest that acute UVB exposure increases the synthesis of retinoic acid in the epidermis. Many of these proteins changed their localization in the epidermis, concentrating in the more differentiated cells of the stratum granulosum and stratum corneum. To determine if retinoic acid was playing a role in repair from UVB light, we examined the changes in proliferation and terminal differentiation markers, keratin 6 and loricrin respectively, with disulfiram treatments, which inhibit retinoic acid synthesis. We found that retinoic acid synthesis is necessary for normal UVB repair. To further explore the role endogenous retinoids play in the formation and progression of cSCC, we examined STRA6, DHRS9, and ALDH1A1 expression using IHC in all tumor stages of cSCC. We found that these proteins change expression throughout cSCC development and may be contributing to changes in retinoic acid synthesis. Changes in endogenous retinoid metabolism in the progression of cSCC may explain why some retinoid treatments have been effective in treating this cancer. These findings may contribute to the development of more effective prevention and treatments for cSCC.
Helen Everts, PhD (Advisor)
Tatiana Oberyszyn, PhD (Committee Member)
Earl Harrison, PhD (Committee Member)
96 p.

Recommended Citations

Citations

  • Gressel, K. L. (2015). Alterations in Endogenous Retinoids with Acute UVB Exposure and in the Progression of Cutaneous Squamous Cell Carcinoma [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429785553

    APA Style (7th edition)

  • Gressel, Katherine. Alterations in Endogenous Retinoids with Acute UVB Exposure and in the Progression of Cutaneous Squamous Cell Carcinoma. 2015. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1429785553.

    MLA Style (8th edition)

  • Gressel, Katherine. "Alterations in Endogenous Retinoids with Acute UVB Exposure and in the Progression of Cutaneous Squamous Cell Carcinoma." Master's thesis, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429785553

    Chicago Manual of Style (17th edition)