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Genetic Variation and Foxp3 Expression in Prostate Tumor

Genetic Variation and Foxp3 Expression in Prostate Tumor


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About the Book

Prostate cancer is the most common cancer of men in Europe, North America and parts of Africa, and a leading cause of death among men in the United States and Western Europe. Some studies suggest a more aggressive cancer in African-American men than in white men. The reason for the disparity is not completely known, however there may be several biological factors involved including variation in immune system activity. FOXP3 expression has been shown to be increased in several cancers, mostly as a function of the increased numbers of regulatory T (Treg) cells in peripheral blood and at the site of the tumor. FOXP3 is a member of the forkhead family of transcription factors that are involved in several cellular processes. Within the natural Treg cell, FOXP3 is responsible for up-regulation of several genes involved in suppression of effector T cells. Recently, FOXP3 has been shown to be expressed in cancer cells. The major objective of this study was to investigate the effect of FOXP3 expression changes in prostate tumor cells with a focus on polymorphisms in conserved regulatory regions as the agents of change. The study found that polymorphisms in a conserved region of intron 1 that are variable only in African and African-American populations were significantly associated with the Gleason score as an intermediate marker of tumor aggression (p=0.047). At least one of the polymorphisms (rs6609859) results in an additional NFAT binding site in intron 1 of the FOXP3 gene which may lead to up-regulation of FOXP3 expression. In vitro studies of FOXP3 over-expression in tumor used quantitative PCR to examine mRNA expression of selected genes. These studies suggest increased proliferative, survival, and suppressive capability of FOXP3 expressing tumor cells through up-regulation of expression of key genes including CTLA-4 and c-Myc. Future studies should investigate the in-vivo effects of FOXP3 expressing tumor cells.


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Product Details
  • ISBN-13: 9781243628626
  • Publisher: Proquest, Umi Dissertation Publishing
  • Publisher Imprint: Proquest, Umi Dissertation Publishing
  • Height: 254 mm
  • Weight: 259 gr
  • ISBN-10: 1243628626
  • Publisher Date: 01 Sep 2011
  • Binding: Paperback
  • Spine Width: 8 mm
  • Width: 203 mm


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