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. © 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.
| Original language | English |
|---|---|
| Pages (from-to) | 4074-4089 |
| Number of pages | 16 |
| Journal | Cancer |
| Volume | 118 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - Aug 15 2012 |
| Externally published | Yes |
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Keywords
- DNA methyltransferase 3b
- esophageal squamous cell carcinoma
- prognosis
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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.
In: Cancer, Vol. 118, No. 16, 15.08.2012, p. 4074-4089.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The role of DNA methyltransferase 3b in esophageal squamous cell carcinoma
AU - Chen, Miao Fen
AU - Lu, Ming Shian
AU - Lin, Paul Yang
AU - Chen, Ping Tsung
AU - Chen, Wen Cheng
AU - Lee, Kuan Der
PY - 2012/8/15
Y1 - 2012/8/15
N2 - 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.
AB - 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.
KW - DNA methyltransferase 3b
KW - esophageal squamous cell carcinoma
KW - prognosis
UR - http://www.scopus.com/inward/record.url?scp=84864643049&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864643049&partnerID=8YFLogxK
U2 - 10.1002/cncr.26736
DO - 10.1002/cncr.26736
M3 - Article
C2 - 22213175
AN - SCOPUS:84864643049
VL - 118
SP - 4074
EP - 4089
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 16
ER -