生物谷报道：据1月12日的《细胞》杂志上的一篇研究报告，美国科学家已经找到了可增加人体内的一种天然抗癌物质的基因，并有望成为未来治愈肿瘤的关键基因。
美国斯隆-凯特琳癌症中心肿瘤生物与遗传学教授Pier Paolo Pandolfi博士与哥伦比亚大学的研究人员们合作，对一种叫做PTEN的肿瘤抑制基因已经进行了多年深入的研究。早在2005年，斯隆-凯特琳中心的研究人员们就曾报道了在另一种叫做P53的肿瘤抑制基因关闭时，该基因甚至仍然可以阻止前列腺癌大肿瘤生长。PTEN基因可通过阻止癌症相关细胞过度增殖和诱导肿瘤细胞死亡来抑制肿瘤。在本质上PTEN基因在细胞内扮演着警卫的角色。但当基因突变时，它将不能很好保护细胞。PTEN基因的突变与数种癌症的发生有关，包括前列腺、脑和乳腺肿瘤。
根据Pandolfi博士在1月12日《细胞》杂志中新发表的三篇文章，他们发现有可能通过修补一种可调节PTEN活性的酶来加强该基因的表达。这种叫做NEDD4-1的酶对调控PTEN的行为起重要作用。如果细胞内这种酶过多，PTEN基因将难以防止癌症。这使得科学家们想搞清楚是否能够通过操控这种酶的水平来控制肿瘤。
Pandolfi博士说，尽管要根据这一发现开发出一种真正的药物还需要很长时间，这种可操控肿瘤抑制基因的能力有可能是一种突破。目前该研究小组正在建立更精密的细胞模型和动物模型以证实这种方法是否有效
Pandolfi补充到，由于增强PTEN基因的作用可能使该基因对健康的细胞造成不良影响，所以针该基因的这种治疗也可能出现不良结果。就像目前的化疗药物在杀死肿瘤的同时，有时对身体也有害一样。
Figure 1. Polyubiquitination of PTEN In Vivo and In Vitro
(A) Polyubiquitination of transfected PTEN. C-terminal His-tagged PTEN was cotransfected with HA-tagged ubiquitin (HA-Ub) in 293T cells as indicated. The cells were treated with or without 25 μM proteasome inhibitor MG132 for 6 hr and then harvested and lysed. His-tagged PTEN was pulled down with Ni2+ beads, washed with 6 M guanidine as described in Experimental Procedures, and subjected to immunoblotting against HA-tag to detect ubiquitinated PTEN.
(B) In vitro ubiquitination of PTEN. The in vitro assay was performed as described in Experimental Procedures with individual components added as indicated. GST-PTEN was used as the substrate, and HS100 (5 μl and 5 mg protein/ml) was required to provide the PTEN ubiquitin ligase (E3) activity.
原文出处：
Cell January 12, 2007: 128 (1)
NEDD4-1 Is a Proto-Oncogenic Ubiquitin Ligase for PTENp129
Xinjiang Wang, Lloyd C. Trotman, Theresa Koppie, Andrea Alimonti, Zhenbang Chen, Zhonghua Gao, Junru Wang, Hediye Erdjument-Bromage, Paul Tempst, Carlos Cordon-Cardo, Pier Paolo Pandolfi, and Xuejun Jiang
[Summary] [Full Text] [PDF] [Supplemental Data]
Ubiquitination Regulates PTEN Nuclear Import and Tumor Suppressionp141
Lloyd C. Trotman, Xinjiang Wang, Andrea Alimonti, Zhenbang Chen, Julie Teruya-Feldstein, Haijuan Yang, Nikola P. Pavletich, Brett S. Carver, Carlos Cordon-Cardo, Hediye Erdjument-Bromage, Paul Tempst, Sung-Gil Chi, Hyo-Jong Kim, Tom Misteli, Xuejun Jiang, and Pier Paolo Pandolfi
[Summary] [Full Text] [PDF] [Supplemental Data]
Essential Role for Nuclear PTEN in Maintaining Chromosomal Integrityp157
Wen Hong Shen, Adayabalam S. Balajee, Jianli Wang, Hong Wu, Charis Eng, Pier Paolo Pandolfi, and Yuxin Yin
[Summary] [Full Text] [PDF] [Supplemental Data]
相关基因：
PTEN
Official Symbol: PTEN and Name: phosphatase and tensin homolog (mutated in multiple advanced cancers 1) [Homo sapiens]
Other Aliases: BZS, MGC11227, MHAM, MMAC1, PTEN1, TEP1
Other Designations: MMAC1 phosphatase and tension homolog deleted on chromosome 10; mutated in multiple advanced cancers 1; phosphatase and tensin homolog; tensin homolog
Chromosome: 10; Location: 10q23.3
MIM: 601728
GeneID: 5728
作者简介：
Pier Paolo Pandolfi, MD, PhD
Head, Molecular and Developmental Biology Laboratory; Albert C. Foster Chair
Dr. Pandolfi is a molecular biologist who, with his colleagues, is studying the molecular genetics of acute myeloid leukemias. In particular, he is working to elucidate the molecular mechanisms underlying the pathogenesis of acute promyelocytic leukemia, by studying the causal role of the chromosomal translocations -- the transfer of genetic material between two different chromosomes as a result of abnormal breakage and refusion -- that are associated with this disease, as well as the normal functions of the genes that are disrupted as a consequence of these translocations. The intent ultimately is to interfere with the genetic changes that lead to these potentially fatal types of cancer. In laboratory studies, the investigators have identified a combination of drugs that induce leukemia cells to mature and behave like normal, healthy cells.
View Pier Paolo Pandolfi's laboratory research at Sloan-Kettering Institute.
