5-Aza-2’deoxycytidine induces BTG2/Tis21/PC3 expression in EJ Bladder carcinoma cells
Devanand, Preethi; Ryu, Min Sook; Lim, In Kyoung
Department of Biochemistry & Molecular Biology, Ajou University School of Medicine
B cell translocation gene 2 (BTG2/Tis21/PC3) belongs to the family of antiproliferative (APRO) genes and reported as a tumor suppressor by our group and others. Expression of BTG2 is significantly reduced in cancers developed in various organs and tissues. EJ human bladder cancer cells containing mutant H-Ras and mutant p53 also reveal loss of BTG2 expression without gene mutation. Therefore, we analyzed epigenetic changes of BTG2 gene such as hypermethylation of CpG islands located in its promoter and intron and changes of chromatin conformation after treatment with 5-Aza 2’deoxycytidine (decitabine). Decitabine induced expressions of BTG2 and Sp1 along with increased binding of Sp1 to CpG islands in BTG2 when analyzed by ChIP assay, which resulted in the significant reduction of growth rate and colony forming ability of EJ cells. Not only EJ cells but also HL-60 human leukemia cells also induced BTG2 expression upon decitabine treatment and regulated differentiation of HL60 cells via degradation of c-Myc protein. Moreover, decitabine treatment failed to induce APRO genes like BTG1, BTG3, BTG4, Tob1 and Tob2. Above data strongly suggest in vivo application of BTG2 induction to regulate cancer cells p53 independent manner.
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