Expression of Aurora kinases A and B in normal, hyperplastic, and malignant human endometrium: Aurora B as a predictor for poor prognosis in endometrial carcinoma

Kurai, Makoto; Shiozawa, Tanri; Shih, Hsien-Chang; Miyamoto, Tsutomu; Feng, Yuemin; Kashima, Hiroyasu; Suzuki, Asuka; Konishi, Ikuo

doi:10.1016/j.humpath.2005.09.014

Cited by 77 publications

(71 citation statements)

References 28 publications

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“…The mechanisms by which aurora B has been proposed to promote tumor progression are loss of mitotic control and abnormal proliferation (7). In this regard, we found a positive correlation between aurora B levels and the tumor proliferation rate assessed by the immunostaining for the early proliferation marker Ki67 (data not shown), similar to the data published for cohorts of astrocytoma (29), endometrial carcinoma (26), and thyroid carcinoma (27).…”

Section: Discussionsupporting

confidence: 89%

“…Although aurora A expression has been studied in many different tumor types (17 -23), aurora B protein expression has received attention only recently in studies on patient material, and has been found overexpressed in primary human colorectal (24), prostate (25), endometrial (26), and thyroid (27) cancers; in seminomas (28); and in astrocytomas (29), at various pathologic stages, with a tendency to group in higher grades of malignancy.…”

Section: Introductionmentioning

confidence: 99%

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Frequent overexpression of aurora B kinase, a novel drug target, in non–small cell lung carcinoma patients

Vischioni

Oudejans²,

Vos³

et al. 2006

Molecular Cancer Therapeutics

117

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The serine/threonine protein kinase aurora B, a key regulator of mitosis, is emerging as a novel drug target for cancer treatment. Aurora B overexpression has been previously documented by immunohistochemistry in several types of human tumors. We assessed aurora B expression in a series of 160 non -small cell lung cancer (NSCLC) samples (60% stage I, 21% stage II, 11% stage III, and 8% stage IV). In addition, we determined the expression of survivin and p16, two molecules also involved in cell cycle control. Aurora B was expressed selectively in tumor cells compared with normal epithelium. Aurora B expression was significantly correlated with expression of survivin in the nucleus (P < 0.0001), but not with expression of p16 (P = 0.134). High aurora B expression levels were significantly associated with older age (P = 0.012), male sex (P = 0.013), squamous cell carcinoma histology (P = 0.001), poor tumor differentiation grade (P = 0.007), and lymph node invasion (P = 0.037), in the subset of radically resected patients in our series. In addition, aurora B expression predicted shorter survival for the patients with adenocarcinoma histology, at both univariate (P = 0.020) and multivariate (P = 0.012) analysis. Survivin expression levels were neither associated with patient clinicopathologic characteristics nor with survival. However, expression of survivin in the nucleus was preferentially detected in stage I and II than in stage III and IV (P = 0.007) in the overall series of NSCLC samples. Taken together, our results suggest that aurora B may represent a valid target in NSCLC. [Mol Cancer Ther 2006;5(11):2905 -13]

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Frequent overexpression of aurora B kinase, a novel drug target, in non–small cell lung carcinoma patients

Vischioni

Oudejans²,

Vos³

et al. 2006

Molecular Cancer Therapeutics

117

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“…After mRNA extraction, reverse transcription and real-time quantitative RT-PCR were carried out in each case. The data were then compared to the immunohistochemical protein expression in matched formalin-fixed and paraffin-embedded tissue (cases [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Various levels of messenger RNA expression of the CHFR were detected in NSCLC (Fig.…”

Section: Correlation Between Mrna and Immunohistochemical Protein Expmentioning

confidence: 99%

“…Overexpression of Aurora-A is evident in a range of primary cancers, such as those of the breast, bladder, esophagus and pancreas, [2][3][4][5][6][7] and its overexpression has been correlated with clinical aggressiveness. [2][3][4][5][6][7] These reports suggest that Aurora-A possesses oncogenic characteristics and plays a key role in cancer progression. However, there is a paucity of data on the relationship between Aurora-A overexpression and the malignant potential of NSCLC.…”

mentioning

confidence: 99%

CHFR expression is preferentially impaired in smoking‐related squamous cell carcinoma of the lung, and the diminished expression significantly harms outcomes

Takeshita

Koga

Takayama

et al. 2008

Intl Journal of Cancer

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Loss of tumor suppressors and activation of oncogenes lead to carcinogenesis. Abnormal expression of CHFR, a novel checkpoint gene, or of Aurora kinases, key regulators of mitosis, has been detected in a variety of solid tumors. Recently, CHFR has been revealed to ensure chromosomal stability by controlling the expression level of Aurora-A in vitro. However, the frequency of aberrant expression of these proteins and the association with clinicopathologic parameters remain poorly defined in nonsmall-cell lung cancer (NSCLC). In this study, we investigated the immunohistochemical protein expression of CHFR and Aurora-A in 157 NSCLC cases and evaluated the association between clinicopathologic parameters statistically. The relationship between CHFR protein and mRNA levels and the association between this relationship and promoter methylation of the CHFR gene were also examined in 20 frozen sections of NSCLC. Overexpression of Aurora-A and reduced expression of CHFR were found in 94 cases (59.8%) and 62 cases (39%) of NSCLC, respectively, and those were significantly correlated with tumor differentiation and size. Moreover, diminished CHFR expression was significantly associated with smoking-related squamous cell carcinoma cases and poor prognosis. Multivariate analysis revealed that CHFR expression was an independent prognostic factor. A statistical correlation was evident between CHFR protein and mRNA expression. In conclusion, our results suggest the aberrant expression of Aurora-A and/or of CHFR contributed to the increase in the malignant potential of NSCLC. We also revealed that CHFR expression was predominantly impaired in smoking-related squamous cell carcinoma and might be a useful prognostic marker in NSCLC.

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“…It is also a protein of the chromosomal passenger complex (CPC), localized on the centromeres from the prophase through to the metaphase-anaphase transition together with Survivin, inner centromere protein (INCENP) and Borealin to regulate segregation and cytokinesis (1)(2)(3)(4)(5). Aurora B is overexpressed in a various types of cancer including thyroid, prostate and endometrial carcinomas, and its upregulation is associated with cell proliferation, prognosis, metastasis and chromosomal number instability to produce multinuclearity (2)(3)(4)(5). Previously, we also found that nuclear Aurora B expression is correlated with cell proliferation, multinuclearity and metastasis in oral cancer (6).…”

Section: Introductionmentioning

confidence: 99%

Nuclear Aurora B and cytoplasmic Survivin expression is involved in lymph node metastasis of colorectal cancer

et al. 2012

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Abstract. The chromosomal passenger complex (CPC) is a key regulator of chromosome segregation and cytokinesis, and consists of Aurora B kinase, INCENP, Survivin and Borealin. Aurora B is a member of a family of serine/threonine protein kinases, and Survivin belongs to the inhibitors of apoptosis (IAP) gene family, and is also a member of the CPC family. Aurora B and Survivin have also been reported to be overexpressed in various human cancers; however, as yet no studies have investigated the co-expression of Survivin and Aurora B in colorectal carcinoma. Therefore, in the present study, the correlation between Aurora B and Survivin expression was investigated using immunohistochemistry and the associated pathological features in colorectal carcinoma were analyzed. Our present findings showed that nuclear Aurora B and cytoplasmic Survivin expression are strongly associated with and involved in lymph node metastasis in colorectal cancer. Therefore, we suggest that nuclear Aurora B and cytoplasmic Survivin are useful diagnostic markers and therapeutic targets in colorectal carcinoma.

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Expression of Aurora kinases A and B in normal, hyperplastic, and malignant human endometrium: Aurora B as a predictor for poor prognosis in endometrial carcinoma

Cited by 77 publications

References 28 publications

Frequent overexpression of aurora B kinase, a novel drug target, in non–small cell lung carcinoma patients

Frequent overexpression of aurora B kinase, a novel drug target, in non–small cell lung carcinoma patients

CHFR expression is preferentially impaired in smoking‐related squamous cell carcinoma of the lung, and the diminished expression significantly harms outcomes

Nuclear Aurora B and cytoplasmic Survivin expression is involved in lymph node metastasis of colorectal cancer

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