生物谷報(bào)道：據(jù)1月12日的《細(xì)胞》雜志上的一篇研究報(bào)告,，美國科學(xué)家已經(jīng)找到了可增加人體內(nèi)的一種天然抗癌物質(zhì)的基因，并有望成為未來治愈腫瘤的關(guān)鍵基因,。
美國斯隆-凱特琳癌癥中心腫瘤生物與遺傳學(xué)教授Pier Paolo Pandolfi博士與哥倫比亞大學(xué)的研究人員們合作,，對(duì)一種叫做PTEN的腫瘤抑制基因已經(jīng)進(jìn)行了多年深入的研究。早在2005年,，斯隆-凱特琳中心的研究人員們就曾報(bào)道了在另一種叫做P53的腫瘤抑制基因關(guān)閉時(shí),，該基因甚至仍然可以阻止前列腺癌大腫瘤生長(zhǎng),。PTEN基因可通過阻止癌癥相關(guān)細(xì)胞過度增殖和誘導(dǎo)腫瘤細(xì)胞死亡來抑制腫瘤,。在本質(zhì)上PTEN基因在細(xì)胞內(nèi)扮演著警衛(wèi)的角色,。但當(dāng)基因突變時(shí),，它將不能很好保護(hù)細(xì)胞,。PTEN基因的突變與數(shù)種癌癥的發(fā)生有關(guān),，包括前列腺、腦和乳腺腫瘤,。
根據(jù)Pandolfi博士在1月12日《細(xì)胞》雜志中新發(fā)表的三篇文章,，他們發(fā)現(xiàn)有可能通過修補(bǔ)一種可調(diào)節(jié)PTEN活性的酶來加強(qiáng)該基因的表達(dá)。這種叫做NEDD4-1的酶對(duì)調(diào)控PTEN的行為起重要作用,。如果細(xì)胞內(nèi)這種酶過多,，PTEN基因?qū)㈦y以防止癌癥,。這使得科學(xué)家們想搞清楚是否能夠通過操控這種酶的水平來控制腫瘤。
Pandolfi博士說,，盡管要根據(jù)這一發(fā)現(xiàn)開發(fā)出一種真正的藥物還需要很長(zhǎng)時(shí)間，這種可操控腫瘤抑制基因的能力有可能是一種突破,。目前該研究小組正在建立更精密的細(xì)胞模型和動(dòng)物模型以證實(shí)這種方法是否有效
Pandolfi補(bǔ)充到,，由于增強(qiáng)PTEN基因的作用可能使該基因?qū)?a href="http://hnhlg.com/news/list-54.html" target="_blank">健康的細(xì)胞造成不良影響，所以針該基因的這種治療也可能出現(xiàn)不良結(jié)果,。就像目前的化療藥物在殺死腫瘤的同時(shí),，有時(shí)對(duì)身體也有害一樣。
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.
原文出處：
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]
相關(guān)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
作者簡(jiǎn)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.
