title: Early upregulation of cyclooxygenase-2 in human papillomavirus type 16 and telomerase-induced immortalization of human esophageal epithelial cells.
abstract: OBJECTIVE
  Cyclooxygenase-2 (COX-2) plays an important role in the carcinogenesis of esophageal squamous cell carcinoma (ESCC). However, it is not clear whether COX-2 is involved in the early or late stage of the development of ESCC. The aim of this study was to investigate the role of COX-2 in the carcinogenesis of ESCC by an immortalized esophageal epithelial cell line.
  
  
  METHODS
  Human papillomavirus type 16 (HPV16)-E6/E7 and human telomerase reverse transcriptase (hTERT) transfection were used for immortalization of esophageal epithelial cells. COX-2-specific RNA interference was used for the inhibition of COX-2 expression.
  
  
  RESULTS
  An immortalized esophageal epithelial cell line, NE6-E6E7/hTERT, was established, which had high proliferation activity but failed to induce colony formation in soft agar. COX-2 expression was upregulated in the early process of immortalization, while COX-2 small interfering RNA (siRNA) decreased the Bcl-2 expression, increased the expression of Bax, and induced cell-cycle arrest at the G0/G1 phase in NE6-E6E7/hTERT cells. Expressions of p53, cyclinD1, and the ratio of hyperphosphorylated-RB/hypophosphorylated-RB were progressively increased after E6E7 and the subsequent hTERT transfections. These changes were accompanied by the alteration of COX-2 expression, but could be reversed by COX-2 siRNA (P < 0.05). P16 expression was significantly downregulated in NE6-E6E7 or NE6-E6E7/hTERT cells (P < 0.05), and was not affected by COX-2 siRNA.
  
  
  CONCLUSIONS
  Our results suggest that induction of cyclooxygenase-2 is essential in the human papillomavirus type 16 and hTERT-induced immortalization of human esophageal epithelial cells, and that COX-2 inhibition may be a potential target to block the carcinogenesis of ESCC at the precancerous stage.
authors: Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fujian, China.
authors: Ze-Hao
authors: ZH
authors: Zhuang
authors: Sai-Wah
authors: SW
authors: Tsao
authors: Wen
authors: W
authors: Deng
authors: Ji-De
authors: JD
authors: Wang
authors: Harry Hua-Xiang
authors: HH
authors: Xia
authors: Hua
authors: H
authors: He
authors: Hui-Chen
authors: HC
authors: Feng
authors: Li-Dong
authors: LD
authors: Wang
authors: Qing
authors: Q
authors: Gu
authors: S-K
authors: SK
authors: Lam
authors: Marie C-M
authors: MC
authors: Lin
authors: Hsiang-Fu
authors: HF
authors: Kung
authors: Benjamin C-Y
authors: BC
authors: Wong
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002472:Cell Transformation, Viral; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology* / Q000473:pathology / Q000821:virology; D004947:Esophagus / Q000201:enzymology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007621:Karyotyping; D014411:Neoplastic Stem Cells / Q000201:enzymology; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C059731:oncogene protein E7, Human papillomavirus type 16; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C509186:TERT protein, human; D019098:Telomerase; D015232:Dinoprostone