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EditRegion1 | Continuing the DNA Methylation Project... DNA methylation is regulated by a family of DNA methyltransferase enzymes (Dnmt-1, Dnmt-3a and Dnmt-3b). Dnmt-1 has been implicated in the aberrant methylation of genes in some tumors including prostate cancer. Specific studies examining Dnmt-1 function in cells has demonstrated an association of Dnmt-1 and cellular transformation including decreased contact inhibition, increased genomic methylation, increased growth in soft agar and increased tumorigenicity. These data suggest that increased DNA methyltransferase levels and activity affect the methylation status of genes critical to tumor formation and progression. We have recently shown that Dnmt-1 is transcriptionally regulated by E2F-1 following the disruption of Rb. We have also shown that prostate tumorigenesis can be dramatically inhibited by the methyltransferase inhibitor, 5-aza-2’deoxycytidine (5-aza), in the TRAMP mouse model of prostate cancer. |
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1. Kuefer R, Hofer MD, Altug V, Zorn C, Genze F, Kunzi-Rapp K, Hautmann RE, Gschwend JE: Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer. Br J Cancer 2004 ; 90(2): 535-41. 2. Kuefer R., Zorn C., Hoefer M., Rubin M. and Day ML. Assessment of a fragment of E- cadherin as a serum biomarker with predictive value for prostate cancer. Br J Cancer. June 6;92(11):2018-23. 2005. 3. R. Kuefer, K. C. Day, C. G. Kleer, M. S. Sabel, M. D. Hofer, S. Varambally, C. S. Zorn, A. M. Chinnaiyan, M. A. Rubin and Mark L. Day. The ADAM15 disintegrin is associated with aggressive prostate and breast cancer disease. Neoplasia. 2006. 8(4): 319-329. |
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