Methylation mediated silencing of TMS1 in breast cancer and its potential contribution to docetaxel cytotoxicity

Edna Gordian, Kavitha Ramachandran, Rakesh Singal

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3207-3210
Number of pages4
JournalAnticancer Research
Volume29
Issue number8
StatePublished - Aug 1 2009

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docetaxel
Methylation
Breast Neoplasms
Genes
Azacitidine
Propidium
Annexin A5
MCF-7 Cells
Tumor Suppressor Genes
Reverse Transcriptase Polymerase Chain Reaction
Apoptosis
Staining and Labeling
Gene Expression
Drug Therapy
Polymerase Chain Reaction

Keywords

  • breast cancer
  • chemotherapy
  • DNA methylation
  • Epigenetics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Methylation mediated silencing of TMS1 in breast cancer and its potential contribution to docetaxel cytotoxicity. / Gordian, Edna; Ramachandran, Kavitha; Singal, Rakesh.

In: Anticancer Research, Vol. 29, No. 8, 01.08.2009, p. 3207-3210.

Research output: Contribution to journalArticle

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