Date of Award

7-1-2013

Degree Type

Dissertation

University or Center

Clark Atlanta University(CAU)

School

School of Arts and Sciences

Degree Name

Ph.D.

Biological Sciences

First Advisor

Dr. Jaideep Chaudhary

Second Advisor

Dr. Shafiq Khan

Third Advisor

Dr. Valarie Odero-Marah

Abstract

Myxovirus (influenza virus) resistance A (MxA) is an interferon regulated protein responsible for a specific antiviral state against viral infection. Our lab has previously shown that MxA is up-regulated by androgens in the normal prostate epithelial cells; however, there is no known role for MxA in cancer. Meta-analysis of different expression databases (e.g. NCBI GEO and Oncomine) suggested a strong inverse association between MxA expression and prostate cancer. To confirm these studies, we performed immunohistochemistry on normal prostate and prostate cancer tissues. Our results revealed that MxA expression was indeed decreased in cancerous as compared to normal prostate, indicating that MxA could be transcriptionally down-regulated in cancer. Previous studies indicated that MxA down-regulation could be due to a specific polymorphism in the proximal MxA promoter at position -88. This single nucleotide polymorphism G>T (rs2071430) is involved in modifying the gene expression and interestingly, it harbors an interferon-stimulated response element (ISRE) that is required for expression in response to interferons. The "T" allele restores whereas the "G" allele attenuates ISRE binding, resulting in increased or decreased MxA expression, respectively. Based on these observations we hypothesized that decreased expression of MxA in prostate cancer could be due to the rs2071430 polymorphism. We investigated this polymorphism in genomic DNA from equal number of disease free and prostate cancer samples. The results provide evidence that the GG genotype (low promoter activity) is higher in PCa (72%) as compared to normal (58.6%). The TT genotype (high activity) was higher in normal (5.7%) compared to PCa (2.4%) p

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