Date of Completion

Spring 5-14-2014

Thesis Advisor(s)

Charles Giardina, Arlene Albert

Honors Major

Biological Sciences

Abstract

Vitamin D is generally known to protect against colon cancer; however, its beneficial effects are limited to early stages in tumorigenesis. Vitamin D binds to the Vitamin D receptor (VDR), which has been shown to meditate colon cancer risk. From previous interventional studies, it has been suggested that VDR is down-regulated in tumorigenic cells leading to the formation of cancer. Potential mechanisms by which VDR is regulated in tumors were studied. Histone deacetylase (HDAC) and Retinoid X receptors (RXR) were studied as potential factors that regulate VDR expression. APC+/∆14 mice treated with Panobinostat, a HDAC inhibitor, and Bexarotene, a RXR agonist, were measured for VDR gene expression along with other VDR target genes. The tumor and normal colon tissue were extracted, followed by a gene expression analysis using a Real-time qPCR. Mice treated with Panobinostat showed a significant increase in the expression of VDR in tumors as compared to normal tissues. This suggests that VDR expression may be regulated with HDACs. Mice treated with Bexarotene did not show a significant increase in VDR expression; RXR might not be limited by the level of the ligand. Even though vitamin D benefits are limited to the early stages in tumor growth, it may be possible to develop therapies that enhance vitamin D effects. The drug Panobinostat has been shown to up-regulate VDR expression in later stages of tumorigenesis in a mouse model.

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