RNA interference targeting aurora kinase A suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells

Tatsuo Hata, Toru Furukawa, Makoto Sunamura, Shinichi Egawa, Fuyuhiko Motoi, Noriyuki Ohmura, Tomotoshi Marumoto, Hideyuki Saya, Akira Horii

Research output: Contribution to journalArticle

190 Citations (Scopus)

Abstract

AURKA/STK15/BTAK, the gene encoding Aurora A kinase that is involved in the regulation of centrosomes and segregation of chromosomes, is frequently amplified and overexpressed in various kinds of human cancers, including pancreatic cancer. To address its possibility as a therapeutic target for pancreatic cancer, we employed the RNA interference technique to knockdown AURKA expression and analyzed its phenotypes. We found that the specific knockdown of AURKA in cultured pancreatic cancer cells strongly suppressed in vitro cell growth and in vivo tumorigenicity. The knockdown induced the accumulation of cells in the G2-M phase and eventual apoptosis. Furthermore, we observed a synergistic enhancement of the cytotoxicity of taxanes, a group of chemotherapeutic agents impairing G2-M transition, by the RNA interference-mediated knockdown of AURKA. These results indicate that inhibition of AURKA expression can result in potent antitumor activity and chemosensitizing activity to taxanes in human pancreatic cancer.

Original languageEnglish
Pages (from-to)2899-2905
Number of pages7
JournalCancer Research
Volume65
Issue number7
DOIs
Publication statusPublished - 2005 Apr 1
Externally publishedYes

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Aurora Kinase A
RNA Interference
Pancreatic Neoplasms
Growth
Taxoids
Neoplasms
Centrosome
Chromosome Segregation
G2 Phase
Cell Division
taxane
Apoptosis
Phenotype
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

RNA interference targeting aurora kinase A suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells. / Hata, Tatsuo; Furukawa, Toru; Sunamura, Makoto; Egawa, Shinichi; Motoi, Fuyuhiko; Ohmura, Noriyuki; Marumoto, Tomotoshi; Saya, Hideyuki; Horii, Akira.

In: Cancer Research, Vol. 65, No. 7, 01.04.2005, p. 2899-2905.

Research output: Contribution to journalArticle

Hata, Tatsuo ; Furukawa, Toru ; Sunamura, Makoto ; Egawa, Shinichi ; Motoi, Fuyuhiko ; Ohmura, Noriyuki ; Marumoto, Tomotoshi ; Saya, Hideyuki ; Horii, Akira. / RNA interference targeting aurora kinase A suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells. In: Cancer Research. 2005 ; Vol. 65, No. 7. pp. 2899-2905.
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AU - Motoi, Fuyuhiko

AU - Ohmura, Noriyuki

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