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Polo样激酶1(PLK1)在原发性结直肠癌中过表达。

Polo-like kinase 1 (PLK1) is overexpressed in primary colorectal cancers.

作者信息

Takahashi Takao, Sano Bun, Nagata Takayasu, Kato Hiroki, Sugiyama Yasuyuki, Kunieda Katsuyuki, Kimura Masashi, Okano Yukio, Saji Shigetoyo

机构信息

Second Department of Surgery, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8705.

出版信息

Cancer Sci. 2003 Feb;94(2):148-52. doi: 10.1111/j.1349-7006.2003.tb01411.x.

Abstract

PLK (polo-like kinase), the human counterpart of polo in Drosophila melanogaster and of CDC5 in Saccharomyces cerevisiae, belongs to a family of serine/threonine kinases. It is intimately involved in spindle formation and chromosome segregation during mitosis. The purpose of this study was to determine whether PLK1 is overexpressed in primary colorectal cancer specimens as compared with normal colon mucosa and to assess its relation to other kinases as a potential new tumor marker. In the present study, immunohistochemical analyses were performed of PLK1 expression in 78 primary colorectal cancers as well as 15 normal colorectal specimens. Furthermore, we examined the relationship between other kinases, Aurora-A and Aurora-C, and PLK1 expression. In normal colon mucosa, some crypt cells showed weakly positive staining for PLK1 in 13 out of 15 cases, the remaining cases being negative. Elevated expression of PLK1 was observed in 57 (73.1%) of the colorectal cancers, statistically significant associations being evident with pT (primary tumor invasion) (P=0.0006, Mann-Whitney U test), pN (regional lymph nodes) (P=0.008, chi2 test) and the Dukes' classification (P=0.0005, Mann-Whitney U test). Mean proliferating cell nuclear antigen-labeling index was 52.3%, with a range of 24.1% to 77.3%. Values for lesions with high and low PLK1 expression were 54.7+/-10.3% (mean+/-SD) and 45.9+/-11.9% (P=0.002, Student's t test). PLK1 was significantly associated with Aurora-A, but PLK1 staining was more diffuse and extensive than for Aurora-A or Aurora-C. Interestingly, PLK1 overexpression was significantly associated with p53 accumulation in colorectal cancers. Our results suggest overexpression of PLK1 might be of pathogenic, prognostic and proliferative importance, so that this kinase might have potential as a new tumor marker for colorectal cancers.

摘要

PLK(类polo激酶)是果蝇中polo以及酿酒酵母中CDC5在人类中的对应物,属于丝氨酸/苏氨酸激酶家族。它在有丝分裂过程中与纺锤体形成和染色体分离密切相关。本研究的目的是确定与正常结肠黏膜相比,原发性结直肠癌标本中PLK1是否过表达,并评估其作为一种潜在的新肿瘤标志物与其他激酶的关系。在本研究中,对78例原发性结直肠癌以及15例正常结直肠标本进行了PLK1表达的免疫组织化学分析。此外,我们还研究了其他激酶Aurora - A和Aurora - C与PLK1表达之间的关系。在正常结肠黏膜中,15例中有13例的一些隐窝细胞对PLK1呈弱阳性染色,其余病例为阴性。在57例(73.1%)结直肠癌中观察到PLK1表达升高,与pT(原发肿瘤浸润)(P = 0.0006,Mann - Whitney U检验)、pN(区域淋巴结)(P = 0.008,卡方检验)以及Dukes分期(P = 0.0005,Mann - Whitney U检验)存在统计学显著关联。平均增殖细胞核抗原标记指数为52.3%,范围为24.1%至77.3%。PLK1高表达和低表达病变的值分别为54.7±10.3%(平均值±标准差)和45.9±11.9%(P = 0.002,Student's t检验)。PLK1与Aurora - A显著相关,但PLK1染色比Aurora - A或Aurora - C更弥漫和广泛。有趣的是,PLK1过表达与结直肠癌中p53积累显著相关。我们的结果表明PLK1过表达可能在致病、预后和增殖方面具有重要意义,因此这种激酶可能有潜力作为结直肠癌的一种新肿瘤标志物。

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