xCT, component of cysteine/glutamate transporter, as an independent prognostic factor in human esophageal squamous cell carcinoma

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• 作者：Atsushi Shiozaki (1)
  Daisuke Iitaka (1)
  Daisuke Ichikawa (1)
  Shingo Nakashima (1)
  Hitoshi Fujiwara (1)
  Kazuma Okamoto (1)
  Takeshi Kubota (1)
  Shuhei Komatsu (1)
  Toshiyuki Kosuga (1)
  Hiroki Takeshita (1)
  Hiroki Shimizu (1)
  Yoshito Nako (1)
  Hisami Sasagawa (2)
  Mitsuo Kishimoto (3)
  Eigo Otsuji (1)
  
• 关键词：xCT/SLC7A11 ; Esophageal cancer ; Cell cycle
• 刊名：Journal of Gastroenterology
• 出版年：2014
• 出版时间：May 2014
• 年：2014
• 卷：49
• 期：5
• 页码：853-863
• 全文大小：
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• 作者单位：Atsushi Shiozaki (1)
  Daisuke Iitaka (1)
  Daisuke Ichikawa (1)
  Shingo Nakashima (1)
  Hitoshi Fujiwara (1)
  Kazuma Okamoto (1)
  Takeshi Kubota (1)
  Shuhei Komatsu (1)
  Toshiyuki Kosuga (1)
  Hiroki Takeshita (1)
  Hiroki Shimizu (1)
  Yoshito Nako (1)
  Hisami Sasagawa (2)
  Mitsuo Kishimoto (3)
  Eigo Otsuji (1)
  
  1. Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan
  2. School of Nursing, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan
  3. Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan
  
• ISSN：1435-5922

文摘

Background xCT is a component of the cysteine/glutamate transporter, which plays a key role in glutathione synthesis. The objectives of the present study were to investigate the role of xCT in the regulation of genes involved in cell cycle progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). Methods xCT expression in human ESCC cell lines was analyzed by Western blotting and immunofluorescent staining. Knockdown experiments were conducted with xCT siRNA, and the effect on cell cycle was analyzed. The cells-gene expression profiles were analyzed by microarray analysis. An immunohistochemical analysis of 70 primary tumor samples obtained from ESCC patients that had undergone esophagectomy was performed. Results xCT was highly expressed in TE13 and KYSE170 cells. In these cells, the knockdown of xCT using siRNA inhibited G1-S phase progression. Microarray analysis identified 1652 genes whose expression levels in TE13 cells were altered by the knockdown of xCT. Pathway analysis showed that the top-ranked canonical pathway was the G1/S checkpoint regulation pathway, which involves TP53INP1, CDKN1A, CyclinD1/cdk4, and E2F5. Immunohistochemical staining showed that xCT is mainly found in the nuclei of carcinoma cells, and that its expression is an independent prognostic factor. Conclusions These observations suggest that the expression of xCT in ESCC cells might affect the G1/S checkpoint and impact on the prognosis of ESCC patients. As a result, we have a deeper understanding of the role played by xCT as a mediator and/or biomarker in ESCC.