Expression of Skp2, a p27Kip1 ubliquitin ligase, in malignant lymphoma:: correlation with p27Kip1 and proliferation index

Expression of Skp2, a p27Kip1 ubliquitin ligase, in malignant lymphoma:: correlation with p27Kip1 and proliferation index
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DOI:
10.1182/blood.v100.8.2950
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发表时间:
2002-10-15
期刊:
影响因子:
20.3
通讯作者:
Elenitoba-Johnson, KSJ
Elenitoba-Johnson, KSJ
中科院分区:
医学1区
文献类型:
--
作者:
Lim, MS;Adamson, A;Elenitoba-Johnson, KSJ

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p27(Kip 1)水平降低在人类癌症中很常见,并且与预后不良有关。Skp 2是Skp 1-Cul 1-F-box蛋白(SCF)泛素连接酶复合物的一个组分,与p27(Kip 1)降解有关。在一些实体瘤中观察到Skp 2水平升高,并与p27(Kip 1)降低相关。我们研究了这些蛋白质的表达,使用单和双免疫标记在一个大的系列淋巴瘤,以确定其相对水平的变化是否与细胞增殖和淋巴瘤亚组的变化;我们研究了Skp 2在低度和侵袭性B细胞淋巴瘤(n=86)的表达,并将其与p27(Kip 1)和增殖指数(PI)进行比较。对15个造血细胞系和外周血淋巴细胞进行了Western印迹分析。在反应性扁桃体中,Skp 2表达仅限于增殖的生发中心和滤泡间细胞。Skp 2在小淋巴细胞性淋巴瘤(SLL)和滤泡性淋巴瘤(FCL)中的表达较低(平均阳性肿瘤细胞百分比小于20%),且与肿瘤大小呈负相关(r=-0.67; P
Reduced levels of p27(Kip1) are frequent in human cancers and have been associated with poor prognosis. Skp2, a component of the Skp1-Cul1-F-box protein (SCF) ubiquitin ligase complex, has been implicated in p27(Kip1) degradation. Increased Skp2 levels are seen in some solid tumors and are associated with reduced p27(Kip1). We examined the expression of these proteins using single and double immunolabeling in a large series of lymphomas to determine if alterations in their relative levels are associated with changes in cell proliferation and lymphoma subgroups; We studied the expression of Skp2 in low-grade and aggressive B-cell lymphomas (n=86) and compared them with p27(Kip1) and the proliferation index (PI). Fifteen hematopoietic cell lines and peripheral blood lymphocytes were studied by Western blot analysis. In reactive tonsils, Skp2 expression was limited to proliferating germinal center and interfollicular cells. Skp2 expression in small lymphocytic lymphomas (SLLs) and follicular lymphomas (FCLs) was low (mean percentage of positive tumor cells, less than 20%) and was inversely correlated (r=-0.67; P