Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IκBα overexpression

Makoto Sumitomo, Masaaki Tachibana, Choichiro Ozu, Hirotaka Asakura, Masaru Murai, Masamichi Hayakawa, Hiroshi Nakamura, Atsushi Takayanagi, Nobuyoshi Shimizu

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

We investigated whether the cell growth and apoptosis of multiple cytokine-producing bladder cancer cells can be regulated by nuclear factor κB (NF-κB). The bladder cancer cell line KU-19-19, obtained from a 76-year-old man who demonstrated marked leukocytosis, produces multiple cytokines and demonstrates autocrine growth by granulocyte colony-stimulating factor (G-CSF). Electrophoretic mobility shift assay (EMSA) revealed that NF-κB was activated in KU-19-19 but not in other bladder cancer cell lines (KU-1, KU-7, or T-24, respectively). The inhibition of NF-κB DNA-binding activity with adenovirus vectors expressing the stable form of the NF-κB inhibitor IκBα (multiplicity of infection [MOI] of 10) inhibited growth and induced apoptosis of KU-19-19, but not KU-1, KU-7, or T-24. The production of several cytokines was suppressed significantly in KU-19-19 by this gene delivery. Although dexamethasone (10 μM) could also suppress cytokine production, it did not induce dramatic cell death in KU-19-19 because it could not inhibit NF-κB activation stably and strongly. These results suggest that NF-κB activation maintains the cell viability as well as regulates cytokine production in cytokine-producing cancer cells and therefore these in vitro experiments support a rationale for preclinical in vivo studies to demonstrate growth inhibition in established tumors.

Original languageEnglish
Pages (from-to)37-47
Number of pages11
JournalHuman Gene Therapy
Volume10
Issue number1
DOIs
Publication statusPublished - 1999 Jan 1

Fingerprint

Urinary Bladder Neoplasms
Adenoviridae
Apoptosis
Cytokines
Growth
Cell Line
Leukocytosis
Electrophoretic Mobility Shift Assay
Granulocyte Colony-Stimulating Factor
Dexamethasone
Neoplasms
Cell Survival
Cell Death
DNA
Infection
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Sumitomo, M., Tachibana, M., Ozu, C., Asakura, H., Murai, M., Hayakawa, M., ... Shimizu, N. (1999). Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IκBα overexpression. Human Gene Therapy, 10(1), 37-47. https://doi.org/10.1089/10430349950019174

Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IκBα overexpression. / Sumitomo, Makoto; Tachibana, Masaaki; Ozu, Choichiro; Asakura, Hirotaka; Murai, Masaru; Hayakawa, Masamichi; Nakamura, Hiroshi; Takayanagi, Atsushi; Shimizu, Nobuyoshi.

In: Human Gene Therapy, Vol. 10, No. 1, 01.01.1999, p. 37-47.

Research output: Contribution to journalArticle

Sumitomo, M, Tachibana, M, Ozu, C, Asakura, H, Murai, M, Hayakawa, M, Nakamura, H, Takayanagi, A & Shimizu, N 1999, 'Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IκBα overexpression', Human Gene Therapy, vol. 10, no. 1, pp. 37-47. https://doi.org/10.1089/10430349950019174
Sumitomo, Makoto ; Tachibana, Masaaki ; Ozu, Choichiro ; Asakura, Hirotaka ; Murai, Masaru ; Hayakawa, Masamichi ; Nakamura, Hiroshi ; Takayanagi, Atsushi ; Shimizu, Nobuyoshi. / Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IκBα overexpression. In: Human Gene Therapy. 1999 ; Vol. 10, No. 1. pp. 37-47.
@article{321a87a14cc347f7b1376b0b56543863,
title = "Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IκBα overexpression",
abstract = "We investigated whether the cell growth and apoptosis of multiple cytokine-producing bladder cancer cells can be regulated by nuclear factor κB (NF-κB). The bladder cancer cell line KU-19-19, obtained from a 76-year-old man who demonstrated marked leukocytosis, produces multiple cytokines and demonstrates autocrine growth by granulocyte colony-stimulating factor (G-CSF). Electrophoretic mobility shift assay (EMSA) revealed that NF-κB was activated in KU-19-19 but not in other bladder cancer cell lines (KU-1, KU-7, or T-24, respectively). The inhibition of NF-κB DNA-binding activity with adenovirus vectors expressing the stable form of the NF-κB inhibitor IκBα (multiplicity of infection [MOI] of 10) inhibited growth and induced apoptosis of KU-19-19, but not KU-1, KU-7, or T-24. The production of several cytokines was suppressed significantly in KU-19-19 by this gene delivery. Although dexamethasone (10 μM) could also suppress cytokine production, it did not induce dramatic cell death in KU-19-19 because it could not inhibit NF-κB activation stably and strongly. These results suggest that NF-κB activation maintains the cell viability as well as regulates cytokine production in cytokine-producing cancer cells and therefore these in vitro experiments support a rationale for preclinical in vivo studies to demonstrate growth inhibition in established tumors.",
author = "Makoto Sumitomo and Masaaki Tachibana and Choichiro Ozu and Hirotaka Asakura and Masaru Murai and Masamichi Hayakawa and Hiroshi Nakamura and Atsushi Takayanagi and Nobuyoshi Shimizu",
year = "1999",
month = "1",
day = "1",
doi = "10.1089/10430349950019174",
language = "English",
volume = "10",
pages = "37--47",
journal = "Human Gene Therapy",
issn = "1043-0342",
publisher = "Mary Ann Liebert Inc.",
number = "1",

}

TY - JOUR

T1 - Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IκBα overexpression

AU - Sumitomo, Makoto

AU - Tachibana, Masaaki

AU - Ozu, Choichiro

AU - Asakura, Hirotaka

AU - Murai, Masaru

AU - Hayakawa, Masamichi

AU - Nakamura, Hiroshi

AU - Takayanagi, Atsushi

AU - Shimizu, Nobuyoshi

PY - 1999/1/1

Y1 - 1999/1/1

N2 - We investigated whether the cell growth and apoptosis of multiple cytokine-producing bladder cancer cells can be regulated by nuclear factor κB (NF-κB). The bladder cancer cell line KU-19-19, obtained from a 76-year-old man who demonstrated marked leukocytosis, produces multiple cytokines and demonstrates autocrine growth by granulocyte colony-stimulating factor (G-CSF). Electrophoretic mobility shift assay (EMSA) revealed that NF-κB was activated in KU-19-19 but not in other bladder cancer cell lines (KU-1, KU-7, or T-24, respectively). The inhibition of NF-κB DNA-binding activity with adenovirus vectors expressing the stable form of the NF-κB inhibitor IκBα (multiplicity of infection [MOI] of 10) inhibited growth and induced apoptosis of KU-19-19, but not KU-1, KU-7, or T-24. The production of several cytokines was suppressed significantly in KU-19-19 by this gene delivery. Although dexamethasone (10 μM) could also suppress cytokine production, it did not induce dramatic cell death in KU-19-19 because it could not inhibit NF-κB activation stably and strongly. These results suggest that NF-κB activation maintains the cell viability as well as regulates cytokine production in cytokine-producing cancer cells and therefore these in vitro experiments support a rationale for preclinical in vivo studies to demonstrate growth inhibition in established tumors.

AB - We investigated whether the cell growth and apoptosis of multiple cytokine-producing bladder cancer cells can be regulated by nuclear factor κB (NF-κB). The bladder cancer cell line KU-19-19, obtained from a 76-year-old man who demonstrated marked leukocytosis, produces multiple cytokines and demonstrates autocrine growth by granulocyte colony-stimulating factor (G-CSF). Electrophoretic mobility shift assay (EMSA) revealed that NF-κB was activated in KU-19-19 but not in other bladder cancer cell lines (KU-1, KU-7, or T-24, respectively). The inhibition of NF-κB DNA-binding activity with adenovirus vectors expressing the stable form of the NF-κB inhibitor IκBα (multiplicity of infection [MOI] of 10) inhibited growth and induced apoptosis of KU-19-19, but not KU-1, KU-7, or T-24. The production of several cytokines was suppressed significantly in KU-19-19 by this gene delivery. Although dexamethasone (10 μM) could also suppress cytokine production, it did not induce dramatic cell death in KU-19-19 because it could not inhibit NF-κB activation stably and strongly. These results suggest that NF-κB activation maintains the cell viability as well as regulates cytokine production in cytokine-producing cancer cells and therefore these in vitro experiments support a rationale for preclinical in vivo studies to demonstrate growth inhibition in established tumors.

UR - http://www.scopus.com/inward/record.url?scp=0032961680&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032961680&partnerID=8YFLogxK

U2 - 10.1089/10430349950019174

DO - 10.1089/10430349950019174

M3 - Article

C2 - 10022529

AN - SCOPUS:0032961680

VL - 10

SP - 37

EP - 47

JO - Human Gene Therapy

JF - Human Gene Therapy

SN - 1043-0342

IS - 1

ER -