Chen J, Willingham T, Shuford M, Nisen P D
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, 75235, USA.
J Clin Invest. 1996 Apr 15;97(8):1983-8. doi: 10.1172/JCI118631.
To investigate how overexpression of p27KIP1, 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 p27KIP1 gene (Adp27KIP1) into the human astrocytoma cell line, U-373MG. Inhibition of CDK activity in Adp27KIP1-infected cells was indicated by inhibition of [3H]thymidine incorporation, an increase in cell doubling time and by cell cycle arrest in G1. Notably, ectopic overexpression of p27KIP1 was associated with a marked decrease in the accumulation of aneuploid cells. Diminished malignant potential of Adp27KIP1-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 p27KIP1 is a tumor suppressor gene and supports the use of Adp27KIP1 for gene therapy of human brain tumors.
为了研究转化生长因子-β的下游效应分子及通用细胞周期蛋白依赖性激酶（CDK）抑制剂p27KIP1的过表达如何影响人恶性脑肿瘤细胞的恶性表型，采用腺病毒载体系统将人p27KIP1基因（Adp27KIP1）导入人星形细胞瘤细胞系U-373MG。[3H]胸腺嘧啶核苷掺入受抑制、细胞倍增时间延长以及细胞周期停滞于G1期均表明Adp27KIP1感染的细胞中CDK活性受到抑制。值得注意的是，p27KIP1的异位过表达与非整倍体细胞积累的显著减少相关。Adp27KIP1感染的细胞恶性潜能降低表现为在软琼脂中失去非锚定依赖性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p27KIP1是一种肿瘤抑制基因，并支持将Adp27KIP1用于人脑肿瘤的基因治疗。
