GLI-mediated Keratin 17 expression promotes tumor cell growth through the anti-apoptotic function in oral squamous cell carcinomas

研究成果: ジャーナルへの寄稿記事

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Purpose: Keratin 17 (KRT17) has been suggested as a potential diagnostic marker of squamous cell carcinoma including oral squamous cell carcinoma (OSCC). The current study was conducted to clarify the function of KRT17 and its expression mechanism in OSCC. Methods: Immunohistochemical analyses were carried out to examine the expression of KRT17, GLI family zinc finger (GLI)-1, GLI-2, or cleaved caspase-3 in OSCCs. The expression of KRT17, GLI-1, or GLI-2 was investigated among OSCC cell lines, and the effects of loss-of-function of KRT17 or GLI, using siRNA or inhibitor, on the cell growth of the OSCC cell line HSC-2 particularly with respect to apoptosis were examined. Results: Immunohistochemical analyses of tissue specimens obtained from 78 OSCC patients revealed that KRT17 was not observed in non-tumor regions but was strongly expressed at high frequencies in tumor regions. Knockdown of KRT17 increased the number of cleaved caspase-3-positive cells, leading to the reduction of cell number. Loss-of-function of GLI-1 or GLI-2 also increased the cell numbers of apoptotic cells positive for staining of Annexin-V and propidium iodide (PI) and the terminal deoxynucleotidyl transferase dUTP-biotin nick-end labeling (TUNEL) method, and induced DNA fragmentation. This inhibitory effect on cell growth was partially rescued by exogenous KRT17 expression. In the KRT17-positive regions in OSCCs, GLI-1 or GLI-2 was frequently detected, and the number of cells with cleaved caspase-3 positive was decreased. Conclusions: KRT17 promotes tumor cell growth, at least partially, through its anti-apoptotic effect as a result of the KRT17 overexpression by GLIs in OSCC.

元の言語英語
ページ(範囲)1381-1393
ページ数13
ジャーナルJournal of Cancer Research and Clinical Oncology
143
発行部数8
DOI
出版物ステータス出版済み - 8 1 2017

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Keratin-17
Squamous Cell Carcinoma
Growth
Neoplasms
Caspase 3
Cell Count
Cell Line
Growth Inhibitors
DNA Nucleotidylexotransferase
Propidium
Annexin A5
Zinc Fingers
DNA Fragmentation
Biotin
Small Interfering RNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

@article{cb7390078ab24ef59d640f843495867c,
title = "GLI-mediated Keratin 17 expression promotes tumor cell growth through the anti-apoptotic function in oral squamous cell carcinomas",
abstract = "Purpose: Keratin 17 (KRT17) has been suggested as a potential diagnostic marker of squamous cell carcinoma including oral squamous cell carcinoma (OSCC). The current study was conducted to clarify the function of KRT17 and its expression mechanism in OSCC. Methods: Immunohistochemical analyses were carried out to examine the expression of KRT17, GLI family zinc finger (GLI)-1, GLI-2, or cleaved caspase-3 in OSCCs. The expression of KRT17, GLI-1, or GLI-2 was investigated among OSCC cell lines, and the effects of loss-of-function of KRT17 or GLI, using siRNA or inhibitor, on the cell growth of the OSCC cell line HSC-2 particularly with respect to apoptosis were examined. Results: Immunohistochemical analyses of tissue specimens obtained from 78 OSCC patients revealed that KRT17 was not observed in non-tumor regions but was strongly expressed at high frequencies in tumor regions. Knockdown of KRT17 increased the number of cleaved caspase-3-positive cells, leading to the reduction of cell number. Loss-of-function of GLI-1 or GLI-2 also increased the cell numbers of apoptotic cells positive for staining of Annexin-V and propidium iodide (PI) and the terminal deoxynucleotidyl transferase dUTP-biotin nick-end labeling (TUNEL) method, and induced DNA fragmentation. This inhibitory effect on cell growth was partially rescued by exogenous KRT17 expression. In the KRT17-positive regions in OSCCs, GLI-1 or GLI-2 was frequently detected, and the number of cells with cleaved caspase-3 positive was decreased. Conclusions: KRT17 promotes tumor cell growth, at least partially, through its anti-apoptotic effect as a result of the KRT17 overexpression by GLIs in OSCC.",
author = "Yurie Mikami and Shinsuke Fujii and Kengo Nagata and Hiroko Wada and Kana Hasegawa and Misaki Abe and Yoshimoto, {Reiko U.} and Shintarou Kawano and Seiji Nakamura and Tamotsu Kiyoshima",
year = "2017",
month = "8",
day = "1",
doi = "10.1007/s00432-017-2398-2",
language = "English",
volume = "143",
pages = "1381--1393",
journal = "Journal of Cancer Research and Clinical Oncology",
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TY - JOUR

T1 - GLI-mediated Keratin 17 expression promotes tumor cell growth through the anti-apoptotic function in oral squamous cell carcinomas

AU - Mikami, Yurie

AU - Fujii, Shinsuke

AU - Nagata, Kengo

AU - Wada, Hiroko

AU - Hasegawa, Kana

AU - Abe, Misaki

AU - Yoshimoto, Reiko U.

AU - Kawano, Shintarou

AU - Nakamura, Seiji

AU - Kiyoshima, Tamotsu

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Purpose: Keratin 17 (KRT17) has been suggested as a potential diagnostic marker of squamous cell carcinoma including oral squamous cell carcinoma (OSCC). The current study was conducted to clarify the function of KRT17 and its expression mechanism in OSCC. Methods: Immunohistochemical analyses were carried out to examine the expression of KRT17, GLI family zinc finger (GLI)-1, GLI-2, or cleaved caspase-3 in OSCCs. The expression of KRT17, GLI-1, or GLI-2 was investigated among OSCC cell lines, and the effects of loss-of-function of KRT17 or GLI, using siRNA or inhibitor, on the cell growth of the OSCC cell line HSC-2 particularly with respect to apoptosis were examined. Results: Immunohistochemical analyses of tissue specimens obtained from 78 OSCC patients revealed that KRT17 was not observed in non-tumor regions but was strongly expressed at high frequencies in tumor regions. Knockdown of KRT17 increased the number of cleaved caspase-3-positive cells, leading to the reduction of cell number. Loss-of-function of GLI-1 or GLI-2 also increased the cell numbers of apoptotic cells positive for staining of Annexin-V and propidium iodide (PI) and the terminal deoxynucleotidyl transferase dUTP-biotin nick-end labeling (TUNEL) method, and induced DNA fragmentation. This inhibitory effect on cell growth was partially rescued by exogenous KRT17 expression. In the KRT17-positive regions in OSCCs, GLI-1 or GLI-2 was frequently detected, and the number of cells with cleaved caspase-3 positive was decreased. Conclusions: KRT17 promotes tumor cell growth, at least partially, through its anti-apoptotic effect as a result of the KRT17 overexpression by GLIs in OSCC.

AB - Purpose: Keratin 17 (KRT17) has been suggested as a potential diagnostic marker of squamous cell carcinoma including oral squamous cell carcinoma (OSCC). The current study was conducted to clarify the function of KRT17 and its expression mechanism in OSCC. Methods: Immunohistochemical analyses were carried out to examine the expression of KRT17, GLI family zinc finger (GLI)-1, GLI-2, or cleaved caspase-3 in OSCCs. The expression of KRT17, GLI-1, or GLI-2 was investigated among OSCC cell lines, and the effects of loss-of-function of KRT17 or GLI, using siRNA or inhibitor, on the cell growth of the OSCC cell line HSC-2 particularly with respect to apoptosis were examined. Results: Immunohistochemical analyses of tissue specimens obtained from 78 OSCC patients revealed that KRT17 was not observed in non-tumor regions but was strongly expressed at high frequencies in tumor regions. Knockdown of KRT17 increased the number of cleaved caspase-3-positive cells, leading to the reduction of cell number. Loss-of-function of GLI-1 or GLI-2 also increased the cell numbers of apoptotic cells positive for staining of Annexin-V and propidium iodide (PI) and the terminal deoxynucleotidyl transferase dUTP-biotin nick-end labeling (TUNEL) method, and induced DNA fragmentation. This inhibitory effect on cell growth was partially rescued by exogenous KRT17 expression. In the KRT17-positive regions in OSCCs, GLI-1 or GLI-2 was frequently detected, and the number of cells with cleaved caspase-3 positive was decreased. Conclusions: KRT17 promotes tumor cell growth, at least partially, through its anti-apoptotic effect as a result of the KRT17 overexpression by GLIs in OSCC.

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U2 - 10.1007/s00432-017-2398-2

DO - 10.1007/s00432-017-2398-2

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