Tumor suppression and inhibition of aneuploid cell accumulation in human brain tumor cells by ectopic overexpression of the cyclin-dependent kinase inhibitor p27(KIP1)
Tumor suppression and inhibition of aneuploid cell accumulation in human brain tumor cells by ectopic overexpression of the cyclin-dependent kinase inhibitor p27(KIP1)
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DOI：
10.1172/jci118631
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发表时间：
1996-04-15
影响因子：
15.9
通讯作者：
Nisen, PD
中科院分区：
文献类型：
--
作者：
Chen, J;Willingham, T;Nisen, PD
为了研究TGF-β下游效应子和通用性细胞周期蛋白依赖性激酶（CDK）抑制剂p27（KIP 1）的过表达如何影响恶性人脑肿瘤细胞的恶性表型，使用腺病毒载体系统将人p27（KIP 1）基因（Adp 27（KIP 1））转移到人星形细胞瘤细胞系U-373 MG中。在Adp 27（KIP 1）感染的细胞中，CDK活性的抑制通过[H-3]胸苷掺入的抑制、细胞倍增时间的增加和G（1）中的细胞周期停滞来表示。值得注意的是，异位过表达p27（KIP 1）与非整倍体细胞的积累显着减少。Adp 27（KIP 1）感染细胞的恶性潜力降低，表现为在软琼脂中失去非贴壁生长以及在异种移植模型中无法诱导肿瘤发生。这些研究表明，p27（KIP 1）是一个肿瘤抑制基因，并支持使用Adp 27（KIP 1）的基因治疗人脑肿瘤。
To investigate how overexpression of p27(KIP1), a downstream effector of TGF-beta and a universal cyclin-dependent kinase (CDK) inhibitor could influence the malignant phenotype of malignant human brain tumor cells, an adenovirus vector system was used to transfer the human p27(KIP1) gene (Adp27(KIP1)) into the human astrocytoma cell line, U-373MG. Inhibition of CDK activity in Adp27(KIP1)-infected cells was indicated by inhibition of [H-3]thymidine incorporation, an increase in cell doubling time and by cell cycle arrest in G(1). Notably, ectopic overexpression of p27(KIP1) was associated with a marked decrease in the accumulation of aneuploid cells. Diminished malignant potential of Adp27(KIP1)-infected cells was manifested by the loss of anchorage-independent growth in soft agar and by the inability to induce tumorgenesis in a xenograft model. These studies suggest that p27(KIP1) is a tumor suppressor gene and supports the use of Adp27(KIP1) for gene therapy of human brain tumors.