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.
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.
Authors: Thomas Clozel; ShaoNing Yang; Rebecca L Elstrom; Wayne Tam; Peter Martin; Matthias Kormaksson; Samprit Banerjee; Aparna Vasanthakumar; Biljana Culjkovic; David W Scott; Sarah Wyman; Micheal Leser; Rita Shaknovich; Amy Chadburn; Fabrizio Tabbo; Lucy A Godley; Randy D Gascoyne; Katherine L Borden; Giorgio Inghirami; John P Leonard; Ari Melnick; Leandro Cerchietti Journal: Cancer Discov Date: 2013-08-16 Impact factor: 39.397
Authors: Daniel D Von Hoff; Drew W Rasco; Elisabeth I Heath; Pamela N Munster; Jan H M Schellens; Nicolas Isambert; Christophe Le Tourneau; Bert O'Neil; Ron H J Mathijssen; Jose A Lopez-Martin; W Jeff Edenfield; Miguel Martin; Patricia M LoRusso; Gordon L Bray; Jorge DiMartino; Aaron Nguyen; Kejian Liu; Eric Laille; Johanna C Bendell Journal: Clin Cancer Res Date: 2018-05-15 Impact factor: 12.531
Authors: Jean-Pierre Issa; Ignacio I Wistuba; Razelle Kurzrock; David J Stewart; Maria I Nunez; Jaroslav Jelinek; David Hong; Sanjay Gupta Journal: Clin Epigenetics Date: 2014-01-09 Impact factor: 6.551