PT  - JOURNAL ARTICLE
AU  - EDNA GORDIAN
AU  - KAVITHA RAMACHANDRAN
AU  - RAKESH SINGAL
TI  - Methylation Mediated Silencing of TMS1 in Breast Cancer and its Potential Contribution to Docetaxel Cytotoxicity
DP  - 2009 Aug 01
TA  - Anticancer Research
PG  - 3207--3210
VI  - 29
IP  - 8
4099  - http://ar.iiarjournals.org/content/29/8/3207.short
4100  - http://ar.iiarjournals.org/content/29/8/3207.full
SO  - Anticancer Res2009 Aug 01; 29
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.