RT Journal Article
SR Electronic
T1 Methylation Mediated Silencing of TMS1 in Breast Cancer and its Potential Contribution to Docetaxel Cytotoxicity
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3207
OP 3210
VO 29
IS 8
A1 EDNA GORDIAN
A1 KAVITHA RAMACHANDRAN
A1 RAKESH SINGAL
YR 2009
UL http://ar.iiarjournals.org/content/29/8/3207.abstract
AB Background: The tumor suppressor gene TMS1 (target of methylation-induced silencing) has been described in the literature as a pro-apoptotic gene. This study examined the methylation status of TMS1 in breast cancer cells and its potential role in sensitivity to docetaxel chemotherapy. Materials and Methods: Methylation of the TMS1 promoter was examined by methylation-specific PCR (MS-PCR) and gene expression was analyzed by reverse transcriptase PCR (RT-PCR). Apoptosis was evaluated by annexin V/propidium iodide staining followed by flow cytometric analysis. Results and Conclusion: The TMS1 promoter was unmethylated in ZR75-1, MB-231 and MCF7 cells which expressed the gene and partially methylated in SKBR3 and Hs578t cells in which TMS1 expression was down-regulated. Treatment of SKBR3 and Hs578t cells with demethylating agents resulted in reactivation of the TMS1 gene. Pretreatment with 5-azacytidine increased sensitivity to docetaxel treatment in SKBR3 and Hs578t cells, indicating that TMS1 reactivation in these cells may contribute to docetaxel sensitivity.