Aurora kinase A has a significant role as a therapeutic target and clinical biomarker in endometrial cancer

Kiyoko Umene, Megumi Yanokura, Kouji Banno, Haruko Irie, Masataka Adachi, Miho Iida, Kanako Nakamura, Yuya Nogami, Kenta Masuda, Yusuke Kobayashi, Eiichirou Tominaga, Daisuke Aoki

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

aurora kinase a (aurKa) regulates the cell cycle checkpoint and maintains genomic integrity. aurKa is overexpressed in various malignant tumors and its upregulation induces chromosomal instability, which leads to aneuploidy and cell transformation. to investigate the role of aurKa in endometrial cancer, we evaluated the association of immunohistochemical expression of aurKa with clinicopathological factors. furthermore, we examined the effects of aurKa inhibition by transfected sirna in Hec-1B cells on colony-forming ability, invasion and migration capacity, and chemosensitivity. immunohistochemical staining showed that overexpression of AURKA was significantly associated with tumor grade (P<0.05) and poor histologic differentiation (P<0.05). the recurrence rate also tended to be high in cases with overexpression of aurKa (P<0.1) and these cases also had a tendency for shorter disease-free survival (DfS) (P<0.1). aurKa inhibition in endometrial cancer cell lines significantly decreased cell growth, invasion and migration (P<0.05), and increased chemosensitivity to paclitaxel. We also evaluated the efficacy of a combination of AURKA siRNA and paclitaxel against subcutaneous tumors formed in a nude mouse. After treatment, the tumor volume shrank significantly compared to treatment with paclitaxel only (P<0.05). to our knowledge, this is the first study in endometrial carcinoma to show a correlation between overexpression of aurKa and tumor grade, histological type and sensitivity to paclitaxel. aurKa is a promising therapeutic target in endometrial cancer and the combination therapy with aurKa inhibitors and paclitaxel could be effective for endometrial cancer that is resistant to conventional treatment and has a poor prognosis.

Original languageEnglish
Pages (from-to)1498-1506
Number of pages9
JournalInternational Journal of Oncology
Volume46
Issue number4
DOIs
Publication statusPublished - 2015 Apr 1

Fingerprint

Aurora Kinases
Aurora Kinase A
Endometrial Neoplasms
Biomarkers
Paclitaxel
Therapeutics
Neoplasms
Chromosomal Instability
Aneuploidy
Cell Cycle Checkpoints
Tumor Burden
Nude Mice
Small Interfering RNA
Disease-Free Survival
Up-Regulation

Keywords

  • Aurora kinase a
  • Chemosensitivity
  • Endometrial cancer
  • Paclitaxel

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Aurora kinase A has a significant role as a therapeutic target and clinical biomarker in endometrial cancer. / Umene, Kiyoko; Yanokura, Megumi; Banno, Kouji; Irie, Haruko; Adachi, Masataka; Iida, Miho; Nakamura, Kanako; Nogami, Yuya; Masuda, Kenta; Kobayashi, Yusuke; Tominaga, Eiichirou; Aoki, Daisuke.

In: International Journal of Oncology, Vol. 46, No. 4, 01.04.2015, p. 1498-1506.

Research output: Contribution to journalArticle

Umene, Kiyoko ; Yanokura, Megumi ; Banno, Kouji ; Irie, Haruko ; Adachi, Masataka ; Iida, Miho ; Nakamura, Kanako ; Nogami, Yuya ; Masuda, Kenta ; Kobayashi, Yusuke ; Tominaga, Eiichirou ; Aoki, Daisuke. / Aurora kinase A has a significant role as a therapeutic target and clinical biomarker in endometrial cancer. In: International Journal of Oncology. 2015 ; Vol. 46, No. 4. pp. 1498-1506.
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AU - Iida, Miho

AU - Nakamura, Kanako

AU - Nogami, Yuya

AU - Masuda, Kenta

AU - Kobayashi, Yusuke

AU - Tominaga, Eiichirou

AU - Aoki, Daisuke

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AB - aurora kinase a (aurKa) regulates the cell cycle checkpoint and maintains genomic integrity. aurKa is overexpressed in various malignant tumors and its upregulation induces chromosomal instability, which leads to aneuploidy and cell transformation. to investigate the role of aurKa in endometrial cancer, we evaluated the association of immunohistochemical expression of aurKa with clinicopathological factors. furthermore, we examined the effects of aurKa inhibition by transfected sirna in Hec-1B cells on colony-forming ability, invasion and migration capacity, and chemosensitivity. immunohistochemical staining showed that overexpression of AURKA was significantly associated with tumor grade (P<0.05) and poor histologic differentiation (P<0.05). the recurrence rate also tended to be high in cases with overexpression of aurKa (P<0.1) and these cases also had a tendency for shorter disease-free survival (DfS) (P<0.1). aurKa inhibition in endometrial cancer cell lines significantly decreased cell growth, invasion and migration (P<0.05), and increased chemosensitivity to paclitaxel. We also evaluated the efficacy of a combination of AURKA siRNA and paclitaxel against subcutaneous tumors formed in a nude mouse. After treatment, the tumor volume shrank significantly compared to treatment with paclitaxel only (P<0.05). to our knowledge, this is the first study in endometrial carcinoma to show a correlation between overexpression of aurKa and tumor grade, histological type and sensitivity to paclitaxel. aurKa is a promising therapeutic target in endometrial cancer and the combination therapy with aurKa inhibitors and paclitaxel could be effective for endometrial cancer that is resistant to conventional treatment and has a poor prognosis.

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