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

Umene K, Yanokura M, Banno K, Irie H, Adachi M, Iida M, Nakamura K, Nogami Y, Masuda K, Kobayashi Y, Tominaga E, Aoki D - Int. J. Oncol. (2015)

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.

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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Effects of Aurora kinase A (AURKA) siRNA transfection on chemosensitivity in HEC-1B cells. (A–C) HEC-1B cells were treated with various concentrations of paclitaxel, cisplatin or adriamycin with or without AURKA siRNA transfection. Percent survival was determined 48 h after administration of anticancer drugs using a Cell Counting kit.
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f4-ijo-46-04-1498: Effects of Aurora kinase A (AURKA) siRNA transfection on chemosensitivity in HEC-1B cells. (A–C) HEC-1B cells were treated with various concentrations of paclitaxel, cisplatin or adriamycin with or without AURKA siRNA transfection. Percent survival was determined 48 h after administration of anticancer drugs using a Cell Counting kit.

Mentions: Recent reports showed that the upregulation of AURKA contributes to chemoresistance in a human cell line, pancreatic esophageal, breast and colon carcinoma cells (22–26). To determine whether AURKA knockdown had an effect on chemosensitivity, a cytotoxicity assay was performed to measure IC50 values of paclitaxel, adriamycin, and cisplatin, which are widely used in gynecological cancer chemotherapy, before and after AURKA knockdown in HEC-1B cells. Only the IC50 for paclitaxel changed after AURKA knockdown (Fig. 4, Table II), indicating that AURKA expression is correlated with sensitivity to paclitaxel. These results suggest that AURKA siRNA and paclitaxel in combination may be effective for treatment of endometrial cancer.


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

Umene K, Yanokura M, Banno K, Irie H, Adachi M, Iida M, Nakamura K, Nogami Y, Masuda K, Kobayashi Y, Tominaga E, Aoki D - Int. J. Oncol. (2015)

Effects of Aurora kinase A (AURKA) siRNA transfection on chemosensitivity in HEC-1B cells. (A–C) HEC-1B cells were treated with various concentrations of paclitaxel, cisplatin or adriamycin with or without AURKA siRNA transfection. Percent survival was determined 48 h after administration of anticancer drugs using a Cell Counting kit.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356503&req=5

f4-ijo-46-04-1498: Effects of Aurora kinase A (AURKA) siRNA transfection on chemosensitivity in HEC-1B cells. (A–C) HEC-1B cells were treated with various concentrations of paclitaxel, cisplatin or adriamycin with or without AURKA siRNA transfection. Percent survival was determined 48 h after administration of anticancer drugs using a Cell Counting kit.
Mentions: Recent reports showed that the upregulation of AURKA contributes to chemoresistance in a human cell line, pancreatic esophageal, breast and colon carcinoma cells (22–26). To determine whether AURKA knockdown had an effect on chemosensitivity, a cytotoxicity assay was performed to measure IC50 values of paclitaxel, adriamycin, and cisplatin, which are widely used in gynecological cancer chemotherapy, before and after AURKA knockdown in HEC-1B cells. Only the IC50 for paclitaxel changed after AURKA knockdown (Fig. 4, Table II), indicating that AURKA expression is correlated with sensitivity to paclitaxel. These results suggest that AURKA siRNA and paclitaxel in combination may be effective for treatment of endometrial cancer.

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.

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.

Show MeSH
Related in: MedlinePlus