Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells.

Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells.
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DOI:
10.1038/sj.bjc.6690826
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发表时间:
1999-12
影响因子:
8.8
通讯作者:
Hoban PR
Hoban PR
中科院分区:
医学1区
文献类型:
--
作者:
Dhar KK;Branigan K;Parkes J;Howells RE;Hand P;Musgrove C;Strange RC;Fryer AA;Redman CW;Hoban PR

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应用免疫组织化学方法对81例上皮性卵巢癌肿瘤切片细胞周期蛋白D1的表达进行了分析。超过10%的肿瘤细胞过表达cyclin D1的肿瘤被认为是阳性的。因此,在72/81例(89%)的检查病例中观察到cyclin D1过表达。24/81(30%)的肿瘤在细胞核和细胞质中均检测到蛋白,48/81(59%)的肿瘤仅在细胞质中检测到蛋白。Cyclin D1在交界性和侵袭性肿瘤中均过表达。蛋白过表达与肿瘤分期和分化无相关性。此外,cyclin D1表达与临床预后无相关性。然而,在过表达cyclin D1的肿瘤中(n = 72),浆液组织中蛋白完全胞浆定位的比例高于非浆液组织(P = 0.004,优势比4.8,95%可信区间为1.4-19.1)。Western分析使用cyclin D1单克隆抗体在7个肿瘤的匀浆中鉴定出一个36kda蛋白,其中一个肿瘤显示细胞核和细胞质免疫染色。采用限制性内切片段长度多态性聚合酶链反应和pcr -多重分析,在1/29细胞周期蛋白D1过表达的肿瘤中检测到细胞周期蛋白D1基因(CCNDI)扩增。我们得出结论,CCND1表达失调导致细胞质和核蛋白定位是卵巢癌中常见的事件,主要发生在缺乏基因扩增的情况下。©1999癌症研究运动
The expression of cyclin D1 protein in tumour sections from 81 patients with epithelial ovarian cancer was analysed using immunohistochemistry. The tumours that overexpressed cyclin D1 in more than 10% of neoplastic cells were considered positive. Thus overexpression of cyclin D1 was observed in 72/81 (89%) of the cases examined. Protein was detected in both the nucleus and the cytoplasm in 24/81 (30%) and localized exclusively in the cytoplasm in 48/81 (59%) of the tumours. Cyclin D1 was overexpressed in both borderline and invasive tumours. There was no association between protein overexpression and tumour stage and differentiation. Furthermore, no correlation between cyclin D1 expression and clinical outcome was observed. However, in tumours overexpressing cyclin D1 (n = 72), the proportion displaying exclusively cytoplasmic localization of protein was higher in those with serous compared with non-serous histology (P = 0.004, odds ratio 4.8, 95% confidence interval 1.4–19.1). Western analysis using a monoclonal antibody to cyclin D1 identified a 36 kDa protein in homogenates from seven tumours displaying cytoplasmic only and one tumour demonstrating both nuclear and cytoplasmic immunostaining. Using restriction fragment length polymorphism polymerase chain reaction and PCR-multiplex analysis, amplification of the cyclin D1 gene (CCNDI) was detected in 1/29 of the tumours demonstrating overexpression of cyclin D1 protein. We conclude that deregulation of CCND1 expression leading to both cytoplasmic and nuclear protein localization is a frequent event in ovarian cancer and occurs mainly in the absence of gene amplification. © 1999 Cancer Research Campaign
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