Genomic imprinting of human p57(KIP2) and its reduced expression in Wilms' tumors
Genomic imprinting of human p57(KIP2) and its reduced expression in Wilms' tumors
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DOI：
10.1093/hmg/5.6.783
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发表时间：
1996-06-01
影响因子：
3.5
通讯作者：
Mukai, T
中科院分区：
文献类型：
--
作者：
Hatada, I;Inazawa, J;Mukai, T
p57（KIP2）是几种G(1)细胞周期蛋白复合物的强效紧密结合抑制剂，是细胞增殖的负调节因子。编码人类p57（KIP2）的基因位于染色体11p15.5上，该区域与散发性癌症和贝克威氏综合征（一种癌症综合征）有关，使其成为肿瘤抑制候选基因。包括Wilms肿瘤、肾上腺皮质癌和横纹肌肉瘤在内的几种类型的儿童肿瘤都表现出母体11p15等位基因的特异性缺失，这表明基因组印记在其中发挥了重要作用。家族性BWS的遗传分析表明，母系携带者可能在基因组印迹中起作用。先前，我们证明p57（KIP2）在小鼠中有印迹。在这里，我们描述了人类p57（KIP2）的基因组印迹及其在Wilms肿瘤中的表达降低。高分辨率定位定位p57（KIP2）在负责肿瘤抑制和BWS的区域。
p57(KIP2) is a potent tight-binding inhibitor of several G(1) cyclin complexes, and is a negative regulator of cell proliferation. The gene encoding human p57(KIP2) is located on chromosome 11p15.5, a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome (BWS), a cancer syndrome, making it a tumor suppressor candidate. Several types of childhood tumors including Wilms' tumor, adrenocortical carcinoma and rhabdomyosarcoma display a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting plays an important part. Genetic analysis of the familial BWS has indicated maternal carriers and suggested a role in genomic imprinting. Previously, we demonstrated that p57(KIP2) is imprinted in the mouse. Here we describe the genomic imprinting of human p57(KIP2) and the reduction of its expression in Wilms' tumors. High resolution mapping locates p57(KIP2) in the region responsible for both tumor suppressivity and BWS.