Downregulation of cytochrome c oxidase 1 induced radioresistance in esophageal squamous cell carcinoma

Tomoko Takesue, Hirofumi Kawakubo, Tetsu Hayashida, Mai Tsutsui, Kazuhiro Miyao, Kazumasa Fukuda, Rieko Nakamura, Tsunehiro Takahashi, Norihito Wada, Hiroya Takeuchi, Yuukou Kitagawa

Research output: Contribution to journalArticle

Abstract

Comprehensive gene screening with transposons is a novel procedure for the systematic identification of resistant genes. The present study aimed to use this technique to identify candidate radioresistant genes in esophageal squamous cell carcinoma. A transposon is a base sequence that can translocate to another location in the genome at random. By inserting the cytomegalovirus promotor as a transcriptional activator in the transposon, the following gene in the new location becomes overexpressed and the gene located at the transposon insertion site is downregulated. Consequently, various transposon-tagged cells, which have differentially overexpressed or downregulated genes using the transposon method can be obtained. Following the irradiation of transposon-tagged cells, candidate radioresistant genes can be selected in order to detect the location of the transposon in the cells that have survived. A total of 11 genes were detected as candidate radioresistant genes. Cytochrome c oxidase 1 (MT-CO1), an enzyme involved in apoptosis through the activation of the caspase cascade, was one of the candidate genes identified. The relative expression level of MT-CO1 was 0.12 in MT-CO1-downregulated cells which was significantly lower compared with the expression level in parent TE4 cells (P<0.001). The survival rate was 28.7% in MT-CO1-downregulated cells and 10.5% in parent TE4 cells 9 days following 5-Gy irradiation. The activity of cytochrome c and caspase-3 following irradiation was significantly lower in the MT-CO1-downregulated radioresistant cells compared with in TE4 cells. In conclusion, the novel gene screening technique demonstrated to be useful for detecting candidate radioresistant genes in esophageal squamous cell carcinoma. The results of the present study revealed that the downregulation of MT-CO1 induced radioresistance occurs by inhibiting the activation of the caspase cascade in radioresistant esophageal cancer cells.

Original languageEnglish
Pages (from-to)4220-4224
Number of pages5
JournalOncology Letters
Volume14
Issue number4
DOIs
Publication statusPublished - 2017

Fingerprint

Cytochromes c1
Electron Transport Complex IV
Down-Regulation
Genes
Caspases
Esophageal Squamous Cell Carcinoma
Esophageal Neoplasms
Cytomegalovirus
Caspase 3

Keywords

  • Cytochrome c oxidase 1
  • Esophageal cancer
  • Gene screening
  • Radioresistance
  • Transposon

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Downregulation of cytochrome c oxidase 1 induced radioresistance in esophageal squamous cell carcinoma. / Takesue, Tomoko; Kawakubo, Hirofumi; Hayashida, Tetsu; Tsutsui, Mai; Miyao, Kazuhiro; Fukuda, Kazumasa; Nakamura, Rieko; Takahashi, Tsunehiro; Wada, Norihito; Takeuchi, Hiroya; Kitagawa, Yuukou.

In: Oncology Letters, Vol. 14, No. 4, 2017, p. 4220-4224.

Research output: Contribution to journalArticle

Takesue, Tomoko ; Kawakubo, Hirofumi ; Hayashida, Tetsu ; Tsutsui, Mai ; Miyao, Kazuhiro ; Fukuda, Kazumasa ; Nakamura, Rieko ; Takahashi, Tsunehiro ; Wada, Norihito ; Takeuchi, Hiroya ; Kitagawa, Yuukou. / Downregulation of cytochrome c oxidase 1 induced radioresistance in esophageal squamous cell carcinoma. In: Oncology Letters. 2017 ; Vol. 14, No. 4. pp. 4220-4224.
@article{61f2e80f1873440cb69685fa173340e0,
title = "Downregulation of cytochrome c oxidase 1 induced radioresistance in esophageal squamous cell carcinoma",
abstract = "Comprehensive gene screening with transposons is a novel procedure for the systematic identification of resistant genes. The present study aimed to use this technique to identify candidate radioresistant genes in esophageal squamous cell carcinoma. A transposon is a base sequence that can translocate to another location in the genome at random. By inserting the cytomegalovirus promotor as a transcriptional activator in the transposon, the following gene in the new location becomes overexpressed and the gene located at the transposon insertion site is downregulated. Consequently, various transposon-tagged cells, which have differentially overexpressed or downregulated genes using the transposon method can be obtained. Following the irradiation of transposon-tagged cells, candidate radioresistant genes can be selected in order to detect the location of the transposon in the cells that have survived. A total of 11 genes were detected as candidate radioresistant genes. Cytochrome c oxidase 1 (MT-CO1), an enzyme involved in apoptosis through the activation of the caspase cascade, was one of the candidate genes identified. The relative expression level of MT-CO1 was 0.12 in MT-CO1-downregulated cells which was significantly lower compared with the expression level in parent TE4 cells (P<0.001). The survival rate was 28.7{\%} in MT-CO1-downregulated cells and 10.5{\%} in parent TE4 cells 9 days following 5-Gy irradiation. The activity of cytochrome c and caspase-3 following irradiation was significantly lower in the MT-CO1-downregulated radioresistant cells compared with in TE4 cells. In conclusion, the novel gene screening technique demonstrated to be useful for detecting candidate radioresistant genes in esophageal squamous cell carcinoma. The results of the present study revealed that the downregulation of MT-CO1 induced radioresistance occurs by inhibiting the activation of the caspase cascade in radioresistant esophageal cancer cells.",
keywords = "Cytochrome c oxidase 1, Esophageal cancer, Gene screening, Radioresistance, Transposon",
author = "Tomoko Takesue and Hirofumi Kawakubo and Tetsu Hayashida and Mai Tsutsui and Kazuhiro Miyao and Kazumasa Fukuda and Rieko Nakamura and Tsunehiro Takahashi and Norihito Wada and Hiroya Takeuchi and Yuukou Kitagawa",
year = "2017",
doi = "10.3892/ol.2017.6699",
language = "English",
volume = "14",
pages = "4220--4224",
journal = "Oncology Letters",
issn = "1792-1074",
publisher = "Spandidos Publications",
number = "4",

}

TY - JOUR

T1 - Downregulation of cytochrome c oxidase 1 induced radioresistance in esophageal squamous cell carcinoma

AU - Takesue, Tomoko

AU - Kawakubo, Hirofumi

AU - Hayashida, Tetsu

AU - Tsutsui, Mai

AU - Miyao, Kazuhiro

AU - Fukuda, Kazumasa

AU - Nakamura, Rieko

AU - Takahashi, Tsunehiro

AU - Wada, Norihito

AU - Takeuchi, Hiroya

AU - Kitagawa, Yuukou

PY - 2017

Y1 - 2017

N2 - Comprehensive gene screening with transposons is a novel procedure for the systematic identification of resistant genes. The present study aimed to use this technique to identify candidate radioresistant genes in esophageal squamous cell carcinoma. A transposon is a base sequence that can translocate to another location in the genome at random. By inserting the cytomegalovirus promotor as a transcriptional activator in the transposon, the following gene in the new location becomes overexpressed and the gene located at the transposon insertion site is downregulated. Consequently, various transposon-tagged cells, which have differentially overexpressed or downregulated genes using the transposon method can be obtained. Following the irradiation of transposon-tagged cells, candidate radioresistant genes can be selected in order to detect the location of the transposon in the cells that have survived. A total of 11 genes were detected as candidate radioresistant genes. Cytochrome c oxidase 1 (MT-CO1), an enzyme involved in apoptosis through the activation of the caspase cascade, was one of the candidate genes identified. The relative expression level of MT-CO1 was 0.12 in MT-CO1-downregulated cells which was significantly lower compared with the expression level in parent TE4 cells (P<0.001). The survival rate was 28.7% in MT-CO1-downregulated cells and 10.5% in parent TE4 cells 9 days following 5-Gy irradiation. The activity of cytochrome c and caspase-3 following irradiation was significantly lower in the MT-CO1-downregulated radioresistant cells compared with in TE4 cells. In conclusion, the novel gene screening technique demonstrated to be useful for detecting candidate radioresistant genes in esophageal squamous cell carcinoma. The results of the present study revealed that the downregulation of MT-CO1 induced radioresistance occurs by inhibiting the activation of the caspase cascade in radioresistant esophageal cancer cells.

AB - Comprehensive gene screening with transposons is a novel procedure for the systematic identification of resistant genes. The present study aimed to use this technique to identify candidate radioresistant genes in esophageal squamous cell carcinoma. A transposon is a base sequence that can translocate to another location in the genome at random. By inserting the cytomegalovirus promotor as a transcriptional activator in the transposon, the following gene in the new location becomes overexpressed and the gene located at the transposon insertion site is downregulated. Consequently, various transposon-tagged cells, which have differentially overexpressed or downregulated genes using the transposon method can be obtained. Following the irradiation of transposon-tagged cells, candidate radioresistant genes can be selected in order to detect the location of the transposon in the cells that have survived. A total of 11 genes were detected as candidate radioresistant genes. Cytochrome c oxidase 1 (MT-CO1), an enzyme involved in apoptosis through the activation of the caspase cascade, was one of the candidate genes identified. The relative expression level of MT-CO1 was 0.12 in MT-CO1-downregulated cells which was significantly lower compared with the expression level in parent TE4 cells (P<0.001). The survival rate was 28.7% in MT-CO1-downregulated cells and 10.5% in parent TE4 cells 9 days following 5-Gy irradiation. The activity of cytochrome c and caspase-3 following irradiation was significantly lower in the MT-CO1-downregulated radioresistant cells compared with in TE4 cells. In conclusion, the novel gene screening technique demonstrated to be useful for detecting candidate radioresistant genes in esophageal squamous cell carcinoma. The results of the present study revealed that the downregulation of MT-CO1 induced radioresistance occurs by inhibiting the activation of the caspase cascade in radioresistant esophageal cancer cells.

KW - Cytochrome c oxidase 1

KW - Esophageal cancer

KW - Gene screening

KW - Radioresistance

KW - Transposon

UR - http://www.scopus.com/inward/record.url?scp=85028926727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028926727&partnerID=8YFLogxK

U2 - 10.3892/ol.2017.6699

DO - 10.3892/ol.2017.6699

M3 - Article

AN - SCOPUS:85028926727

VL - 14

SP - 4220

EP - 4224

JO - Oncology Letters

JF - Oncology Letters

SN - 1792-1074

IS - 4

ER -