Abnormal expression pattern of cyclin E in tumour cells

Abnormal expression pattern of cyclin E in tumour cells
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DOI:
10.1002/ijc.10949
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发表时间:
2003-04-10
影响因子:
6.4
通讯作者:
Zetterberg, A
Zetterberg, A
中科院分区:
医学1区
文献类型:
--
作者:
Erlandsson, F;Wählby, C;Zetterberg, A

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在正常细胞和肿瘤细胞培养和肿瘤活检中研究了细胞周期蛋白E在细胞周期中的表达模式。发现这种模式在肿瘤细胞中是异常的。三重免疫染色协议,数字显微镜和图像分析被用来找到单个细胞在细胞周期中的位置,并测量核细胞周期蛋白E水平。在正常细胞中,当细胞进入S期时,cyclin E阳性细胞的数量迅速减少。在肿瘤细胞系中,细胞周期蛋白E在早期S期没有下调,在正常细胞中。相反,细胞周期蛋白E阳性细胞的数量在整个S期保持高水平,并且每个细胞的细胞周期蛋白E染色强度通常在S期增加。在大约一半的分析的肿瘤细胞系中,许多细胞即使在G(2)期也对细胞周期蛋白E染色阳性。在宫颈癌、乳腺癌和前列腺癌的肿瘤活检中也发现了细胞周期蛋白E在细胞周期中的异常表达,尽管个体肿瘤之间差异很大。在某些肿瘤中,细胞周期蛋白E的表达模式与培养中的正常细胞相似,而在其他肿瘤中,S期细胞中可以看到高水平的细胞周期蛋白E,如在转化细胞系中。在一小部分宫颈癌患者(n = 12)中,发现S期或G(2)期表达细胞周期蛋白E的细胞百分比高与预后差相关(p < 0.025)。(C)2003 Wiley-Liss,Inc.
The expression pattern of cyclin E during the cell cycle was studied in normal and tumour cells in culture and in tumour biopsies. This pattern was found to be abnormal in tumour cells. A triple immunostaining protocol, digital microscopy and image analysis were used to find the position of the individual cells in the cell cycle and to measure the nuclear cyclin E levels. In normal cells, the number of cyclin E-positive cells decreased rapidly when the cells entered the S-phase. In the tumour cell lines, cyclin E was not downregulated in early S-phase, as in normal cells. Instead the number of cyclin E-positive cells remained high throughout S-phase, and the cyclin E staining intensity per cell often increased during S-phase. In about half of the analysed tumour cell lines, many cells stained positive for cyclin E even in the G(2)-phase. This abnormal expression over the cell cycle of cyclin E was also found in tumour biopsies from cervical, breast and prostatic carcinomas, even though it varied greatly between individual tumours. In some tumours, the expression pattern of cyclin E was similar to that of normal cells in culture, whereas in others high cyclin E levels could be seen in S-phase cells, as in the transformed cell lines. A high percentage of cells expressing cyclin E during S- or G(2)-phase was found to be related to poor outcome (p < 0.025) in a small group of cervical carcinoma patients (n = 12). (C) 2003 Wiley-Liss, Inc.