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

研究成果: Article

12 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)1498-1506
ページ数9
ジャーナルInternational Journal of Oncology
46
発行部数4
DOI
出版物ステータスPublished - 2015 4 1

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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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

これを引用

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.

:: International Journal of Oncology, 巻 46, 番号 4, 01.04.2015, p. 1498-1506.

研究成果: Article

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. :: International Journal of Oncology. 2015 ; 巻 46, 番号 4. pp. 1498-1506.
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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.",
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AU - Umene, Kiyoko

AU - Yanokura, Megumi

AU - Banno, Kouji

AU - Irie, Haruko

AU - Adachi, Masataka

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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N2 - 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.

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.

KW - Aurora kinase a

KW - Chemosensitivity

KW - Endometrial cancer

KW - Paclitaxel

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