华人科学家提出重要抑癌基因的新角色

　　

生物通报道：第十号染色体同源丢失性磷酸酶-张力蛋白基因PTEN（phosphatase and tensin homolog deleted on chromosome ten）是一种其蛋白产物具有酪氨酸磷酸酶活性的肿瘤抑制基因，来自著名的美国密苏里州斯托瓦斯医学研究所（Stowers Institute for Medical Research）的华人科学家研究小组发现了这个重要基因的其它以往未知的功能，为进一步解析PTEN作用以及干细胞研究，癌症研究提供了重要资料。这一研究成果公布在4月23日Nature杂志上。

PTEN为1997年发现的抑癌基因，P代表Phosphatase，部分氨基酸序列与细胞骨架蛋白tensin 同源，（Phosphatase and tensin homolog），故缩写命名为PTEN，亦名MMAC1（mutated in multiple advanced caners），与早年P53相仿，亦有人称之为基因卫士。这个基因定位于染色体10q23.3，在子宫内膜癌、神经胶质瘤、前列腺癌、等多种人类原发性恶性肿瘤中存在突变。

PTEN自发现以来已经发现了这种肿瘤抑制基因的生长抑制功能和哺乳动物衰老相关作用，斯托瓦斯研究所的Linheng Li（通讯作者），Jiwang Zhang（第一作者）等研究人员发现PTEN参与的一个体内固有途径能够帮助控制干细胞休眠和激活这两种状态的转换，并且证明干细胞的休眠和进入快速循环这两种极端的状态之间存在“中间激活状态”（intermediate 'activated' state）的重要性。在这个过程中PTEN起着重要作用：决定干细胞是继续细胞循环还是回到休眠G0状态。如果在干细胞中破坏PTEN就会导致更多细胞进入细胞周期，丧失干细胞休眠库（quiescent pool）——这对于长期维持干细胞的特性是必需的。

干细胞为治疗许多人类疾病，包括癌症提出了潜在方案，但是由于成人干细胞来源以及一些道德伦理方面的限制导致了干细胞的应用。以上这一研究也许让我们更加接近了这一期待已久的治疗。（生物通：张迪）

斯托瓦斯研究所（Stowers Institute）

位于密苏里州堪萨斯市，这个60万平方尺的校园里集合了这种先进设施，主要致力于通过进行细胞基本生命过程的研究，寻求尖端技术更有效的预防和治疗疾病。Stowers Institute由Jim Stowers和Virginia Stowers这两位癌症幸存者捐赠的2亿美元资助成立。

Linheng Li

　

　

斯托瓦斯研究所Associate Investigator

主要论著：

Li L, Xie T. Stem Cell Niche: Structure and Function. A nnu Rev Cell Dev Biol. 2005;17:605-631. Abstract

He XC, Zhang J, Li L. Cellular and molecular regulation of hematopoietic and intestinal stem cell behavior. Book Chapter for Ann Rev NY Acad; In: Stem Cell Biology: Development and Plasticity; 2005;1049:28-38. Abstract

Zhang J, Li L. BMP signaling and stem cell regulation. Dev Biol. 2005. Abstract

Li L. Find the Hematopoietic Stem Cell Niche in Placenta. Dev Cell. 2005;8:297-304. Abstract

Tian Q, Feetham MC, Tao W A , He XC, Li L, A ebersold R, Hood L. Proteomic analysis identifies that 14-3-3 {zeta} interacts with {beta} -catenin and facilitates its activation by A kt. Proc Natl A cad Sci U S A . 2004. Abstract

He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, Tian Q, Zeng X, He X, Wiedemann LM, Mishina Y, Li L. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-atenin signaling. Nat Genet. 2004;36:1117-1121. Abstract, The comments regarding this paper News and Views.

Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, Ross J, Haug J, Johnson T, Feng JQ, Harri S, Wiedemann LM, Mishina Y, Li L.. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425:836-841. Abstract, comments regarding this paper News and Views, and a featured article by Nature.

Akashi K, He X, Chen J, Iwasaki H, Niu C, Steenhard B, Zhang J, Haug J and Li L.?Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood. 2003;101.2:383-389. Abstract, The comments regarding this paper Comments.

Park I, He Y, Lin F, Laerum O, Tian Q, Bumgarner R, Klug C, Li K, Kuhr C, Doyle M, Xie X, Schummer M, Sun Y, Goldsmith A, Clarke M, Weissman I, Hood L, Li L.?Differential Gene Expression Profiling of Adult Murine Hematopoietic Stem Cells. Blood. 2002;99:488-498. Abstract

Terskikh AV, Easterday MC, Li L, Hood L, Kornblum HI, Geschwind DH, Weissman IL.?From hematopoiesis to neuropoiesis: evidence of overlapping genetic programs. Proc Natl Acad Sci USA . 2001;98:7934-7939. Abstract.

Li L, Milner L, Deng Y, Iwata W, Banta A, Graf L, Marcovina S, Friedman C, Trask B, Hood L, Torok-Storb B.?The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1. Immunity. 1998; 8:43 -55. Abstract

Li L, Krantz ID, Deng Y, Genin A, Banta A, Collins C, Qi M, Trask BJ, Kuo W, Cochran J, Costa T, Pierpont MEM, Rand EB, Piccoli D, Hood L, Spinner N.?Alagille syndrome is caused by mutations in hJagged1 (JAG1), which encodes a ligand for Notch1. Nature Genetics. 1997;16:243-251. Abstract. Comments regarding this paper News and Views.

Lee TC, Li L, Philipson L, Ziff EB.? Myc represses transcription of the growth arrest gene gas-1. Proc Natl Acad Sci USA . 1997;94:12886-12891. Abstract.

Li L, Nerlov C, Prendergast G, MacGregor D, Ziff EB.?c-Myc represses transcription by a novel mechanism dependent on the initiator element and Myc box II. EMBO J. 1994;13:4070-4079. Abstract.