Adenovirus Expressing p27KIP1 Induces Apoptosis Against Cholangiocarcinoma Cells by Triggering Fas Ligand on the Cell Surface

Kuniharu Yamamoto, Yu Katayose, Masanori Suzuki, Michiaki Unno, Tsuyoshi Sasaki, Masamichi Mizuma, Satoru Shiraso, Hideo Ohtuka, Kenneth H Cowan, Prem Seth, Seiki Matsuno

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Abstract

Background/Aims: The prognosis of patients with cholangiocarcinoma is poor because of the difficulty of surgical curative resection. Therefore, other effective treatments must be developed especially those involving gene therapy. p27kip1, one of the cyclin-dependent kinase inhibitors, is known to limit proliferation of the cells. Our previous reports have shown that the overexpression of p27kip1 by a recombinant adenoviral vector expressing p27kip1 (Adp27) induces apoptosis. However, the mechanism of the Adp27-mediated apoptosis is not still resolved. Activation of the Fas pathway is one of the important gates for apoptosis. In this report, we examined whether p27kip1-induced apoptosis is closely related to the Fas/Fas ligand (FasL) system. Results: After infection of Adp27, flow cytometric analysis showed that Fas ligand was expressed on the cell surface of cholangiocarcinoma cell lines (TFK-1). In spite of detecting the cell surface expression of Fas ligand, overexpression of p27kip1 increased no amount of Fas ligand in mRNA by quantitative RT-PCR and protein level by Western blot. In addition, the immunocytochemical analysis showed that Fas ligand was adequately stored within the cytosol of TFK-1 cells. More interestingly, Adp27-induced apoptosis was completely inhibited by the neutralizing antibody of Fas ligand (NOK-1). This result suggests that overexpression of p27kip1 may deliver Fas ligand to the cell surface and mainly utilizes the Fas pathway as a gate of apoptosis. Conclusions: This is the first report to prove that Adp27-mediated apoptosis utilizes the Fas pathway by delivering Fas ligand to the cell surface.

Original languageEnglish (US)
Pages (from-to)1847-1853
Number of pages7
JournalHepato-Gastroenterology
Volume50
Issue number54
StatePublished - Nov 1 2003

Fingerprint

Fas Ligand Protein
Cholangiocarcinoma
Adenoviridae
Apoptosis
Cyclin-Dependent Kinases
Neutralizing Antibodies
Genetic Therapy
Cytosol
Western Blotting
Cell Proliferation
Cell Line
Polymerase Chain Reaction
Messenger RNA
Infection

Keywords

  • Adenovirus
  • Apoptosis
  • Fas
  • Gene therapy
  • Ligand
  • p27

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Yamamoto, K., Katayose, Y., Suzuki, M., Unno, M., Sasaki, T., Mizuma, M., ... Matsuno, S. (2003). Adenovirus Expressing p27KIP1 Induces Apoptosis Against Cholangiocarcinoma Cells by Triggering Fas Ligand on the Cell Surface. Hepato-Gastroenterology, 50(54), 1847-1853.

Adenovirus Expressing p27KIP1 Induces Apoptosis Against Cholangiocarcinoma Cells by Triggering Fas Ligand on the Cell Surface. / Yamamoto, Kuniharu; Katayose, Yu; Suzuki, Masanori; Unno, Michiaki; Sasaki, Tsuyoshi; Mizuma, Masamichi; Shiraso, Satoru; Ohtuka, Hideo; Cowan, Kenneth H; Seth, Prem; Matsuno, Seiki.

In: Hepato-Gastroenterology, Vol. 50, No. 54, 01.11.2003, p. 1847-1853.

Research output: Contribution to journalArticle

Yamamoto, K, Katayose, Y, Suzuki, M, Unno, M, Sasaki, T, Mizuma, M, Shiraso, S, Ohtuka, H, Cowan, KH, Seth, P & Matsuno, S 2003, 'Adenovirus Expressing p27KIP1 Induces Apoptosis Against Cholangiocarcinoma Cells by Triggering Fas Ligand on the Cell Surface', Hepato-Gastroenterology, vol. 50, no. 54, pp. 1847-1853.
Yamamoto K, Katayose Y, Suzuki M, Unno M, Sasaki T, Mizuma M et al. Adenovirus Expressing p27KIP1 Induces Apoptosis Against Cholangiocarcinoma Cells by Triggering Fas Ligand on the Cell Surface. Hepato-Gastroenterology. 2003 Nov 1;50(54):1847-1853.
Yamamoto, Kuniharu ; Katayose, Yu ; Suzuki, Masanori ; Unno, Michiaki ; Sasaki, Tsuyoshi ; Mizuma, Masamichi ; Shiraso, Satoru ; Ohtuka, Hideo ; Cowan, Kenneth H ; Seth, Prem ; Matsuno, Seiki. / Adenovirus Expressing p27KIP1 Induces Apoptosis Against Cholangiocarcinoma Cells by Triggering Fas Ligand on the Cell Surface. In: Hepato-Gastroenterology. 2003 ; Vol. 50, No. 54. pp. 1847-1853.
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abstract = "Background/Aims: The prognosis of patients with cholangiocarcinoma is poor because of the difficulty of surgical curative resection. Therefore, other effective treatments must be developed especially those involving gene therapy. p27kip1, one of the cyclin-dependent kinase inhibitors, is known to limit proliferation of the cells. Our previous reports have shown that the overexpression of p27kip1 by a recombinant adenoviral vector expressing p27kip1 (Adp27) induces apoptosis. However, the mechanism of the Adp27-mediated apoptosis is not still resolved. Activation of the Fas pathway is one of the important gates for apoptosis. In this report, we examined whether p27kip1-induced apoptosis is closely related to the Fas/Fas ligand (FasL) system. Results: After infection of Adp27, flow cytometric analysis showed that Fas ligand was expressed on the cell surface of cholangiocarcinoma cell lines (TFK-1). In spite of detecting the cell surface expression of Fas ligand, overexpression of p27kip1 increased no amount of Fas ligand in mRNA by quantitative RT-PCR and protein level by Western blot. In addition, the immunocytochemical analysis showed that Fas ligand was adequately stored within the cytosol of TFK-1 cells. More interestingly, Adp27-induced apoptosis was completely inhibited by the neutralizing antibody of Fas ligand (NOK-1). This result suggests that overexpression of p27kip1 may deliver Fas ligand to the cell surface and mainly utilizes the Fas pathway as a gate of apoptosis. Conclusions: This is the first report to prove that Adp27-mediated apoptosis utilizes the Fas pathway by delivering Fas ligand to the cell surface.",
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AU - Suzuki, Masanori

AU - Unno, Michiaki

AU - Sasaki, Tsuyoshi

AU - Mizuma, Masamichi

AU - Shiraso, Satoru

AU - Ohtuka, Hideo

AU - Cowan, Kenneth H

AU - Seth, Prem

AU - Matsuno, Seiki

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AB - Background/Aims: The prognosis of patients with cholangiocarcinoma is poor because of the difficulty of surgical curative resection. Therefore, other effective treatments must be developed especially those involving gene therapy. p27kip1, one of the cyclin-dependent kinase inhibitors, is known to limit proliferation of the cells. Our previous reports have shown that the overexpression of p27kip1 by a recombinant adenoviral vector expressing p27kip1 (Adp27) induces apoptosis. However, the mechanism of the Adp27-mediated apoptosis is not still resolved. Activation of the Fas pathway is one of the important gates for apoptosis. In this report, we examined whether p27kip1-induced apoptosis is closely related to the Fas/Fas ligand (FasL) system. Results: After infection of Adp27, flow cytometric analysis showed that Fas ligand was expressed on the cell surface of cholangiocarcinoma cell lines (TFK-1). In spite of detecting the cell surface expression of Fas ligand, overexpression of p27kip1 increased no amount of Fas ligand in mRNA by quantitative RT-PCR and protein level by Western blot. In addition, the immunocytochemical analysis showed that Fas ligand was adequately stored within the cytosol of TFK-1 cells. More interestingly, Adp27-induced apoptosis was completely inhibited by the neutralizing antibody of Fas ligand (NOK-1). This result suggests that overexpression of p27kip1 may deliver Fas ligand to the cell surface and mainly utilizes the Fas pathway as a gate of apoptosis. Conclusions: This is the first report to prove that Adp27-mediated apoptosis utilizes the Fas pathway by delivering Fas ligand to the cell surface.

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