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.
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 humanesophageal 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.
Authors: Melanie Spitzner; Reinhard Ebner; Hendrik A Wolff; B Michael Ghadimi; Jürgen Wienands; Marian Grade Journal: Cancers (Basel) Date: 2014-09-29 Impact factor: 6.639
Authors: Miao-Fen Chen; Ping-Tsung Chen; Ming Shian Lu; Paul Yang Lin; Wen-Cheng Chen; Kuan-Der Lee Journal: Mol Cancer Date: 2013-04-05 Impact factor: 27.401
Authors: Jasper Wouters; Marguerite Stas; Lies Gremeaux; Olivier Govaere; Anke Van den Broeck; Hannelore Maes; Patrizia Agostinis; Tania Roskams; Joost J van den Oord; Hugo Vankelecom Journal: PLoS One Date: 2013-10-03 Impact factor: 3.240
Authors: Fabio Coppedè; Roberta Ricciardi; Maria Denaro; Anna De Rosa; Carlo Provenzano; Emanuela Bartoccioni; Angelo Baggiani; Marco Lucchi; Alfredo Mussi; Lucia Migliore Journal: PLoS One Date: 2013-11-19 Impact factor: 3.240