Aurora-A kinase is differentially expressed in the nucleus and cytoplasm in normal Müllerian epithelium and benign, borderline and malignant serous ovarian neoplasms.

Aurora-A kinase is differentially expressed in the nucleus and cytoplasm in normal Müllerian epithelium and benign, borderline and malignant serous ovarian neoplasms.
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DOI:
10.1186/s13000-021-01158-4
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发表时间:
2021-10-27
影响因子:
2.6
通讯作者:
Lehman NL
Lehman NL
中科院分区:
医学4区
文献类型:
--
作者:
Alkhateeb KJ;Crane JE;Sak M;Jorgensen CJ;O'Donnell JP;Zumbar CT;Wozniak JA;Salazar CR;Parwani AV;Lehman NL

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Aurora-A 激酶对于细胞增殖很重要,并且与包括卵巢在内的多种恶性肿瘤的发生有关。有关正常苗勒氏管上皮以及良性、交界性和恶性上皮性卵巢肿瘤中 Aurora-A 表达模式的信息有限。我们通过免疫组织化学研究了 15 个良性、19 个交界性和 17 个恶性卵巢浆液性肿瘤,以及 16 个良性、8 个交界性和 2 个恶性卵巢粘液性肿瘤中 Aurora-A 的表达。来自 7 名患者的 12 个菌毛作为正常苗勒氏管上皮对照。我们还通过蛋白质印迹检查了正常菌毛和肿瘤标本中 Aurora-A 蛋白的表达。通过免疫组织化学检测,所有正常菌毛(n = 12)均显示出细胞核而非细胞质的 Aurora-A 免疫反应性。良性卵巢肿瘤也表现出强烈的细胞核 Aurora-A 免疫反应性。 48% (13/27) 的交界性肿瘤表现出核 Aurora-A 免疫反应性,而其余 (52%, 14/27) 缺乏 Aurora-A 染色。所有恶性浆液性肿瘤中均不存在核 Aurora-A 免疫反应性,但 47% (8/17) 表现出核​​周细胞质染色。当肿瘤类别(良性/交界性/恶性)与免疫反应性定位或强度进行比较时,这些结果具有统计学意义(Fisher Exact Test,p<0.01)。蛋白质印迹分析证实,与交界性肿瘤和恶性肿瘤相比,对照苗勒氏管上皮中的核 Aurora-A 表达更高。 Aurora-A 激酶在正常苗勒氏管上皮、良性和交界性浆液性和粘液性卵巢上皮肿瘤以及恶性浆液性卵巢肿瘤中存在差异表达,非磷酸化 Aurora-A 的核表达存在于正常和良性肿瘤上皮中,而在恶性浆液性肿瘤中缺失。有必要进一步研究卵巢肿瘤中核 Aurora-A 表达缺失的可能生物学和临床意义及其在卵巢癌发生中的作用。在线版本包含可在 10.1186/s13000-021-01158-4 获取的补充材料。
Aurora-A kinase is important for cellular proliferation and is implicated in the tumorigenesis of several malignancies, including of the ovary. Information regarding the expression patterns of Aurora-A in normal Müllerian epithelium as well as benign, borderline and malignant epithelial ovarian neoplasms is limited. We investigated Aurora-A expression by immunohistochemistry in 15 benign, 19 borderline and 17 malignant ovarian serous tumors, and 16 benign, 8 borderline, and 2 malignant ovarian mucinous tumors. Twelve fimbriae from seven patients served as normal Müllerian epithelium controls. We also examined Aurora-A protein expression by western blot in normal fimbriae and tumor specimens. All normal fimbriae (n = 12) showed nuclear but not cytoplasmic Aurora-A immunoreactivity by immunohistochemistry. Benign ovarian tumors also showed strong nuclear Aurora-A immunoreactivity. Forty-eight percent (13/27) of borderline tumors demonstrated nuclear Aurora-A immunoreactivity, while the remainder (52%, 14/27) lacked Aurora-A staining. Nuclear Aurora-A immunoreactivity was absent in all malignant serous tumors, however, 47% (8/17) demonstrated perinuclear cytoplasmic staining. These results were statistically significant when tumor class (benign/borderline/malignant) was compared to immunoreactivity localization or intensity (Fisher Exact Test, p < 0.01). Western blot analysis confirmed the greater nuclear Aurora-A expression in control Müllerian epithelium compared to borderline and malignant tumors. Aurora-A kinase is differentially expressed across normal Müllerian epithelium, benign and borderline serous and mucinous ovarian epithelial neoplasms and malignant serous ovarian tumors., with nuclear expression of unphosphorylated Aurora-A being present in normal and benign neoplastic epithelium, and lost in malignant serous neoplasms. Further studies of the possible biological and clinical implications of the loss of nuclear Aurora-A expression in ovarian tumors, and its role in ovarian carcinogenesis are warranted. The online version contains supplementary material available at 10.1186/s13000-021-01158-4.
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