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 language | English |
|---|---|
| Pages (from-to) | 3207-3210 |
| Number of pages | 4 |
| Journal | Anticancer Research |
| Volume | 29 |
| Issue number | 8 |
| State | Published - Aug 1 2009 |
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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 journal › Article
}
TY - JOUR
T1 - Methylation mediated silencing of TMS1 in breast cancer and its potential contribution to docetaxel cytotoxicity
AU - Gordian, Edna
AU - Ramachandran, Kavitha
AU - Singal, Rakesh
PY - 2009/8/1
Y1 - 2009/8/1
N2 - 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.
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.
KW - breast cancer
KW - chemotherapy
KW - DNA methylation
KW - Epigenetics
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UR - http://www.scopus.com/inward/citedby.url?scp=68549087020&partnerID=8YFLogxK
M3 - Article
C2 - 19661336
AN - SCOPUS:68549087020
VL - 29
SP - 3207
EP - 3210
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 8
ER -