The role of DNA methyltransferase 3b in esophageal squamous cell carcinoma

Miao Fen Chen, Ming Shian Lu, Paul Yang Lin, Ping Tsung Chen, Wen Cheng Chen, Kuan Der Lee

研究成果: 雜誌貢獻文章

14 引文 (Scopus)

摘要

BACKGROUND: The identification of potential tumor markers can improve therapeutic planning and patient management. The objective of this study was to highlight the role of DNA methyltransferase 3b (DNMT3b) in esophageal squamous cell carcinoma (SCC). METHODS: One hundred seventy-three esophageal SCC samples were analyzed using immunohistochemical staining to correlate the expression of DNMT3b with clinical outcome. Furthermore, a human esophageal SCC cell line, CE81T, was selected for cellular and animal experiments to investigate changes in tumor behavior and treatment response after the manipulation of DNMT3b expression. RESULTS: The incidence of nuclear DNMT3b immunoreactivity in esophageal cancer specimens was significantly higher than in nonmalignant epithelium, and this incidence was linked positively to developing distant metastasis (56% in localized disease vs 80% in distant metastasis; P =.002). Furthermore, increased expression of DNMT3b was linked significantly to lower treatment response rates (P =.002) and reduced survival rates (P =.000). Inhibition of DNMT3b expression resulted in slower cellular proliferation, increased cell death, a less invasive capacity, and less epithelial-mesenchymal- transition changes. Moreover, DNMT3b silencing vectors sensitized esophageal cancer cells to irradiation and cisplatin treatment. The current results also indicated that constitutional activation of signal transducer and activator of transcription 3 (STAT3) signaling associated with inhibited expression of suppressor of cytokine signaling 3 (SOCS3) may be the mechanism underlying more aggressive tumor growth in DNMT3b-positive esophageal cancer. CONCLUSIONS: DNMT3b was linked significantly to a poor prognosis for patients with esophageal cancer. Moreover, the current results indicated that targeting this enzyme may be a promising strategy for treating esophageal cancer, as evidenced by inhibited aggressive tumor behavior and treatment resistance. Cancer 2012. © 2012 American Cancer Society. The incidence of nuclear DNA methyltransferase 3b (DNMT3b) immunoreactivity in specimens from patients with esophageal cancer is significantly higher than that in nonmalignant epithelium, and this incidence is linked positively to developing distant metastasis and to a poor prognosis. Targeting DNMT3b may be a promising strategy for treating esophageal cancer, as evidenced by inhibited aggressive tumor behavior and treatment resistance.
原文英語
頁(從 - 到)4074-4089
頁數16
期刊Cancer
118
發行號16
DOIs
出版狀態已發佈 - 八月 15 2012
對外發佈Yes

指紋

Esophageal Neoplasms
Incidence
Neoplasms
Neoplasm Metastasis
Esophageal Squamous Cell Carcinoma
DNA methyltransferase 3B
Therapeutics
Epithelium
STAT3 Transcription Factor
Epithelial-Mesenchymal Transition
Tumor Biomarkers
Cisplatin
Cell Death
Survival Rate
Cell Proliferation
Staining and Labeling
Cytokines
Cell Line
Enzymes
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

引用此文

Chen, M. F., Lu, M. S., Lin, P. Y., Chen, P. T., Chen, W. C., & Lee, K. D. (2012). The role of DNA methyltransferase 3b in esophageal squamous cell carcinoma. Cancer, 118(16), 4074-4089. https://doi.org/10.1002/cncr.26736

The role of DNA methyltransferase 3b in esophageal squamous cell carcinoma. / Chen, Miao Fen; Lu, Ming Shian; Lin, Paul Yang; Chen, Ping Tsung; Chen, Wen Cheng; Lee, Kuan Der.

於: Cancer, 卷 118, 編號 16, 15.08.2012, p. 4074-4089.

研究成果: 雜誌貢獻文章

Chen, MF, Lu, MS, Lin, PY, Chen, PT, Chen, WC & Lee, KD 2012, 'The role of DNA methyltransferase 3b in esophageal squamous cell carcinoma', Cancer, 卷 118, 編號 16, 頁 4074-4089. https://doi.org/10.1002/cncr.26736
Chen, Miao Fen ; Lu, Ming Shian ; Lin, Paul Yang ; Chen, Ping Tsung ; Chen, Wen Cheng ; Lee, Kuan Der. / The role of DNA methyltransferase 3b in esophageal squamous cell carcinoma. 於: Cancer. 2012 ; 卷 118, 編號 16. 頁 4074-4089.
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abstract = "BACKGROUND: The identification of potential tumor markers can improve therapeutic planning and patient management. The objective of this study was to highlight the role of DNA methyltransferase 3b (DNMT3b) in esophageal squamous cell carcinoma (SCC). METHODS: One hundred seventy-three esophageal SCC samples were analyzed using immunohistochemical staining to correlate the expression of DNMT3b with clinical outcome. Furthermore, a human esophageal SCC cell line, CE81T, was selected for cellular and animal experiments to investigate changes in tumor behavior and treatment response after the manipulation of DNMT3b expression. RESULTS: The incidence of nuclear DNMT3b immunoreactivity in esophageal cancer specimens was significantly higher than in nonmalignant epithelium, and this incidence was linked positively to developing distant metastasis (56{\%} in localized disease vs 80{\%} in distant metastasis; P =.002). Furthermore, increased expression of DNMT3b was linked significantly to lower treatment response rates (P =.002) and reduced survival rates (P =.000). Inhibition of DNMT3b expression resulted in slower cellular proliferation, increased cell death, a less invasive capacity, and less epithelial-mesenchymal- transition changes. Moreover, DNMT3b silencing vectors sensitized esophageal cancer cells to irradiation and cisplatin treatment. The current results also indicated that constitutional activation of signal transducer and activator of transcription 3 (STAT3) signaling associated with inhibited expression of suppressor of cytokine signaling 3 (SOCS3) may be the mechanism underlying more aggressive tumor growth in DNMT3b-positive esophageal cancer. CONCLUSIONS: DNMT3b was linked significantly to a poor prognosis for patients with esophageal cancer. Moreover, the current results indicated that targeting this enzyme may be a promising strategy for treating esophageal cancer, as evidenced by inhibited aggressive tumor behavior and treatment resistance. Cancer 2012. {\circledC} 2012 American Cancer Society. The incidence of nuclear DNA methyltransferase 3b (DNMT3b) immunoreactivity in specimens from patients with esophageal cancer is significantly higher than that in nonmalignant epithelium, and this incidence is linked positively to developing distant metastasis and to a poor prognosis. Targeting DNMT3b may be a promising strategy for treating esophageal cancer, as evidenced by inhibited aggressive tumor behavior and treatment resistance.",
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