title: Aberrant DNA methylation of T-cell leukemia, homeobox 3 modulates cisplatin sensitivity in bladder cancer.
abstract: The development of resistance to cisplatin during treatment of bladder cancer constitutes a major obstacle to curing bladder cancer. The identification of epigenetic biomarker molecules for cisplatin resistance and the elucidation of the function of the identified genes in bladder cancer will provide useful information. We found that the candidate gene TLX3 was unmethylated in cisplatin sensitive cells and methylated in resistant cells. The suppression of TLX3 expression using TLX3-specific shRNA in parental cells increased cisplatin resistance. Contrarily, overexpression of TLX3 in resistant cells induced increased sensitivity to cisplatin. We found that 22 (21%) out of 110 clinical samples of bladder cancer showed the methylated pattern using the COBRA assay in TLX3. We found a correlation between TLX3 methylation and the sensitivity to cisplatin in the clinical samples by SDI test. Cisplatin sensitivity was closely associated with the methylation status of TLX3. These findings showed that the TLX3 methylation may be useful as a novel biomarker for cisplatin resistance and can be used to design therapies to counteract the resistance against cisplatin in bladder cancer.
authors: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Yasuhiro
authors: Y
authors: Tada
authors: Akira
authors: A
authors: Yokomizo
authors: Masaki
authors: M
authors: Shiota
authors: Toshiyuki
authors: T
authors: Tsunoda
authors: Christoph
authors: C
authors: Plass
authors: Seiji
authors: S
authors: Naito