Wang T J, Huang M S, Hong C Y, Tse V, Silverberg G D, Hsiao M
Department of Pediatrics, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China.
Biochem Biophys Res Commun. 2001 Sep 14;287(1):173-80. doi: 10.1006/bbrc.2001.5565.
The mutation and/or deletion of tumor suppressor genes have been postulated to play a major role in the genesis and the progression of gliomas. In this study, the functional expression and efficacy in tumor suppression of 3 tumor suppressor genes (p53, p21, and p16) were tested and compared in a rat GBM cell line (RT-2) after retrovirus mediated gene delivery in vitro and in vivo. Significant reductions in tumor cell growth rate were found in p16 and p21 infected cells (60 +/- 12% vs 66 +/- 15%) compared to p53 (35 +/- 9%). In vitro colony formation assay also showed significant reductions after p16 and p21 gene delivery (98 +/- 5% vs 91 +/- 10%) compared to p53 (50 +/- 18%). In addition, the tumor suppression efficacy were investigated and compared in vivo. Retroviral mediated p16 and p21 gene deliveries in glioblastomas resulted in more than 90% reductions in tumor growth (92 +/- 26% vs 90 +/- 22%) compared to p53 (62 +/- 18%). Tumor suppressor gene insertions in situ further prolonged animal survival. Overall p16 and p21 genes showed more powerful tumor suppressor effects than p53. The results were not surprising, as p16 and p21 are more downstream in the cell cycle regulatory pathway compared to p53. Moreover, the mechanism involved in each of their suppressor effects is different. This study demonstrates the feasibility of using tumor suppressor genes in regulating the growth of glioma in vitro and in situ.
肿瘤抑制基因的突变和/或缺失被认为在胶质瘤的发生和发展中起主要作用。在本研究中，在体外和体内经逆转录病毒介导的基因传递后，在大鼠胶质母细胞瘤细胞系（RT-2）中测试并比较了3种肿瘤抑制基因（p53、p21和p16）的功能表达及其肿瘤抑制效果。与p53（35±9%）相比，p16和p21感染的细胞中肿瘤细胞生长速率显著降低（60±12%对66±15%）。体外集落形成试验也显示，与p53（50±18%）相比，p16和p21基因传递后集落形成显著减少（98±5%对91±10%）。此外，还在体内研究并比较了肿瘤抑制效果。与p53（62±18%）相比，在胶质母细胞瘤中经逆转录病毒介导的p16和p21基因传递导致肿瘤生长减少90%以上（92±26%对90±22%）。原位插入肿瘤抑制基因进一步延长了动物存活时间。总体而言，p16和p21基因显示出比p53更强的肿瘤抑制作用。结果并不令人意外，因为与p53相比，p16和p21在细胞周期调控途径中更处于下游。此外，它们各自抑制作用所涉及的机制也不同。本研究证明了使用肿瘤抑制基因在体外和原位调节胶质瘤生长的可行性。
