|
  
- 积分
- 4277
- 威望
- 4277
- 包包
- 7646
|
( k% K# j- Z, H7 x& z9 V& L! y$ ?
首先跟大家道歉，本来是昨天晚上应该发的，但临时有事情，一直拖到现在才空出时间来整理。- u# b% c! e. `; f7 v9 c
" ^9 l7 V' z1 Z4 |8 z6 G" i9 T
其实当时我推荐这篇文章的主要理由还是因为 它是 Weinberg RA 写的前沿看法。
; x3 k% S g' i ?0 P4 B4 p# Y4 y& c, ~% E% n2 n
Weinberg RA 这个人，相必对肿瘤研究感兴趣的研究员都应该知道他。
' r% y( {! U$ f* j; D8 ^6 m+ X8 o-----------------------------------------------------------------------------( e( @, u( h: l8 M0 ?3 c
Robert A．Weinberg博士是美国麻省理工学院的生物学教授，美国科学院院士，世界著名的Whitehead研究所创始人之一。他的研究方向为人类肿瘤的遗传学基础，其中最广为人知的是他的实验室发现了第一个人类癌基因Ras和第一个人类抑癌基因Rb。他的一系列杰出研究工作已经成为肿瘤研究领域乃至整个医学生物学领域的重要里程碑。 Weinberg于1969年获得麻省理工学院的博士学位，之后在Weizmann和Salk研究所工作。他作为最主要的领导者之一，于1982年创建了Whitehead研究所。几十年来，Weinberg教授在Nature、Science Cell等国际顶尖科学杂志上发表了一系列高水平的科研论文，他的研究工作和科学理论为肿瘤生物学领域开辟了新的研究方向。
$ ^- m, U; f5 }/ T4 Q' a6 L-----------------------------------------------------------------------------
# t6 n/ m7 ~" D" l5 f1 mWeinberg 实验室介绍：
0 q% g+ W7 D; X' G. E/ m9 ~Weinberg Lab Research Summary, W5 M8 { w, M$ A2 z+ K
Research in our laboratory is focused in several areas: First, how do cancer cells within a primary tumor acquire the ability to invade and metastasize? Second, how are the stem-cell state and the epithelial-mesenchymal transition interrelated? Third, How are the regulators of the epithelial-mesenchymal transition able to activate this profound change in cell phenotype?2 O1 X2 C! t& K. F/ ~) p
. s; K7 K7 H$ J0 b) N% m+ M. \
Acquisition of invasiveness and metastatic powers by cancer cells
4 O, K+ C" q5 zThe ability of cancer cells to invade and metastasize is determined by the genetic changes that these cells have undergone during the course of multi-step tumorigenesis. In addition, the microenvironment of the cancer cell is a strong determinant of whether or not it acquires the capabilities to invade and metastasize. Thus, during the course of primary tumor formation, the cells in a carcinoma will recruit a complex array of mesenchymal cells from the host that together form the tumor-associated stroma. Prominent among these are fibroblasts and myofibroblasts. As tumor progression proceeds, the stromal cells create a "reactive stroma" that releases a variety of signals that impinge on the carcinoma cells and induce changes in their phenotype. We have begun to examine the nature of the signals that are released by this stroma and serve to induce the epithelial-mesenchymal transition (EMT), a profound change in cell phenotype that causes immotile epithelial cells to acquire traits such as motility, invasiveness, and resistance to apoptosis. These signals serve to induce expression of a series of transcription factors that are capable, in turn of inducing the EMT. A significant amount of our research is focused on the nature of these heterotypic signals and how they act, in concert, to induce expression of the EMT-inducing transcription factors in nearby carcinoma cells.
4 e/ p7 o" R I# {& m) C0 t) ?
; g1 C5 U! r8 i# ~The EMT and the stem-cell state5 U3 p8 U. i4 b
Our research has indicated that the act of inducing an EMT (epithelial-mesenchymal transition) in normal and neoplastic mammary epithelial cells results in cells that have acquired many of the attributes of stem cells. Included among these are the expression of cell-surface markers that enable the isolation of stem-cell-like cells. Research into the nature of the EMT-inducing signals (see above) is likely to shed light, as well, on the signals within a stem-cell niche that enable the formation of stem cells and their perpetuation in the stem-cell state. Moreover, by discovering the nature of the stem-cell-inducing signals, we may be able to convert differentiated epithelial cells into epithelial stem cells, which may have important implications for the regeneration of certain epithelial tissues. We believe that the EMT is induced by a group of collaborating signaling molecules. Accordingly, this research is exploring the identities of a variety of signaling proteins that function, in aggregate, to induce an EMT in cancer cells.& j* g, C& V/ v! Y i
0 m/ S, z9 A- a5 X& D+ W" Z3 U
Master regulators of the EMT0 m# A; w! t& M; o' D. b
We have been working with a series of 6-7 transcription factors (TFs) that are expressed transiently during embryogenesis when they program the EMT. These TFs are found to be expressed by invasive and metastatic cells, on which they confer many of the cell phenotypes of high-grade malignancy. In fact, these TFs rarely act alone, but instead intercommunicate and form a complex circuitry that enables them to collaborate to induce the EMT. We are attempting to understand the organization of the signaling circuitry that enable the various EMT-inducing TFs to induce this profound cell-biological change in normal and neoplastic cells. In addition, we are studying the downstream consequences of the actions of these TFs in terms of the genes whose expression they induce and the cell-biological consequences of this induction. We anticipate that gene expression array analyses will allow us to define a core EMT gene expression program that should prove important in understanding the biochemical mechanisms of cancer cell invasion and metastasis and, at the same time, provide indications of useful diagnostic markers to indicate the presence of cells that possess malignant potential within tumors.! ~. ^0 x3 C J6 X
* [. s/ h8 A/ X) O: Z
& O5 u3 J% I& T5 B3 r
Last updated September 2008. |
附件: 你需要登录才可以下载或查看附件。没有帐号？注册
-
总评分: 威望 + 50
包包 + 50
查看全部评分
|
发表于 2009-9-26 20:18
8错8错，顶哦~
发表于 2009-9-26 23:56
