干细胞之家 - 中国干细胞行业门户第一站

 

 

搜索
干细胞之家 - 中国干细胞行业门户第一站 干细胞之家论坛 细胞与微环境 新闻区 沉默两个基因足以将间充质干细胞变为癌起始细胞(附原文 ...
朗日生物

免疫细胞治疗专区

欢迎关注干细胞微信公众号

  
查看: 42865|回复: 12
go

沉默两个基因足以将间充质干细胞变为癌起始细胞(附原文) [复制链接]

Rank: 7Rank: 7Rank: 7

积分
13286 
威望
13286  
包包
34831  

论坛元老 精华勋章 金话筒 专家 优秀会员 优秀版主

楼主
发表于 2011-5-4 10:30 |只看该作者 |倒序浏览 |打印
本帖最后由 细胞海洋 于 2011-5-6 15:18 编辑 9 h! s' `  G! g0 `' d
* ?" n% @9 G) o# F, q
Targeted methylation of two tumor suppressor genes is sufficient to transform mesenchymal stem cells into cancer stem/initiating cells
, P4 X+ g9 O' k  `2 O甲基化沉默两个肿瘤抑制基因足以将间充质干细胞变为癌起始细胞(CSC,CIC)
$ c7 _8 v1 _9 H. S5 X: B8 XCancer research http://cancerres.aacrjournals.or ... AN-10-3418.abstract
$ K! X& a  e1 c& }$ M$ z) b! y" L/ V7 ]. W( f4 ^" w
I-Wen Teng1, Pei-Chi Hou1, Kuan-Der Lee2, Pei-Yi Chu3, Kun-Tu Yeh4, Victor X. Jin5, Min-Jen Tseng1, Shaw-Jenq Tsai6, Yu-Sun Chang Dr.7, Chi-sheng Wu8, H. Sunny Sun9, Kuen-daw Tsai10, Long-Bin Jeng10, Kenneth P. Nephew11, Tim H. M. Huang12, Shu-Huei Hsiao13, , and Yu-Wei Leu14 0 _2 P/ [# o+ x0 \+ x' ^
+ Author Affiliations
8 Z4 x5 {4 E2 |1 t8 o
0 b: `! I7 k) C9 J# B+ n/ p1Department of Life Science, National Chung Cheng University
, L$ T; J( E7 Z0 z- c2Hematology and Oncology, Chang Gung Memorial Hospital
# P8 z7 Z- e4 K3Pathology, ChangHua Christian Hospital
+ k/ r0 J( l- t, E4 Q  ^' s7 J( l4Department of Pathology, Changhua Christian Hospital
4 v( Q9 q- q) N/ s, F& i& f5Biomedical Informatics, The Ohio State University
, r. W: F% }8 i3 j2 J' v: m6Department of Physiology, National Cheng Kung University 9 b2 q* L$ W+ s2 B: E4 v* Z
7Graduate Institute of Basic Medical Sciences, Chang-Gung University
# t$ v5 M1 m6 a8 ^) F! F7 m8Molecular Medicine Research Center, Chang Gung University 9 T0 y, S$ ]( U) C4 F1 W
9National Cheng-Kung University Medical College, Institute of Molecular medicine
2 v9 j$ c: ~/ o' |10Department of Internal Medicine, China Medical University Peikang Hospital 9 \' J  h# X+ E4 p" g
11Cellular and Integrative Physiology, Indiana University ! {( r) K" V9 g; s( m1 _" e1 \
12Human Cancer Genetics, MVIMG Dept, The Ohio State University
9 T+ q8 n% p+ i2 c+ C8 q' e3 {13Life Science, National Chung Cheng University
: c; w, i, I1 e2 |4 B1 k8 x: d14Chung-Cheng University
' i1 Q" f. Z5 }) V  |+ r Corresponding Author:$ }5 I" M* z8 p, i- U  d6 L4 `
Shu-Huei Hsiao, Life Science, National Chung Cheng University, 168 University Road, Min Hsiung, Chia-Yi, 621, Taiwan bioshh@ccu.edu.tw $ j) s# |/ ], R; J% F" J
Abstract
/ ~/ ^" v' Y( y0 S% K' j9 O) x  |Although DNA hypermethylation within promoter CpG islands is highly correlated with tumorigenesis, it has not been established whether DNA hypermethylation within a specific tumor suppressor gene (TSG) is sufficient to fully transform a somatic stem cell. In this study, we addressed this question using a novel targeted DNA methylation technique to methylate the promoters of HIC1 and RassF1A, two well-established TSGs, along with a two-component reporter system to visualize successful targeting of human bone marrow-derived mesenchymal stem cells (MSC) as a model cell system. MSCs harboring targeted promoter methylations of HIC1/RassF1A displayed several features of cancer initiating/cancer stem cells, including loss of anchorage dependence, increased colony formation capability, drug resistance and pluripotency. Notably, inoculation of immunodeficient mice with low numbers of targeted MSC resulted in tumor formation, and subsequent serial xenotransplantation and immunohistochemistry confirmed the presence of stem cell markers and MSC lineage in tumor xenografts. Consistent with the expected mechanism of TSG hypermethylation, treatment of the targeted MSC with a DNA methyltransferase inhibitor reversed their tumorigenic phenotype. To our knowledge, this is the first direct demonstration that aberrant TSG hypermethylation is sufficient to transform a somatic stem cell into a fully malignant cell with cancer initiating/cancer stem properties. 6 T7 Z9 Y; p) }9 ~

6 P7 C2 @6 F$ M- ^0 _8 U6 OReceived September 17, 2010.
8 ~8 B$ t- e+ eRevision received March 27, 2011. 6 w8 R9 L0 z# u3 u% d
Accepted April 18, 2011. " {) K2 ]7 z1 E, V& O* W
Copyright © 2011, American Association for Cancer Research.
5 B) J: R: f) l
6 g) B: H8 D1 ~2 C7 w3 i1 C! u0 q/ x  X0 C
6楼原文 感谢apengforever 提供
已有 1 人评分威望 包包 收起 理由
细胞海洋 + 2 + 10 极好资料

总评分: 威望 + 2  包包 + 10   查看全部评分

Rank: 7Rank: 7Rank: 7

积分
13286 
威望
13286  
包包
34831  

论坛元老 精华勋章 金话筒 专家 优秀会员 优秀版主

沙发
发表于 2011-5-4 11:35 |只看该作者
Tumor Suppressor Methylation is Cause for Cancer Concern
8 V) W3 L& i& Phttp://www.epigenie.com/Headline ... e-cancer-cells.html
/ b; l7 H% b* n9 I7 k2 u8 bMay 2, 2011 Aberrant DNA methylation causes cancer.  Wait, didn’t we know this already? Well, not exactly. Association and causation are two very different things. For instance, being smart may be associated with wearing glasses, but the actual cause is a desire to not bump into everything.
7 a# R6 y+ t* N0 k9 z8 l; d. D' Q, y) h6 M
In order to determine whether aberrant DNA methylation at particular loci can play a causal role in tumorigenesis, a team of researchers from Taiwan and Ohio developed a novel method.  Here is how they did it and what they found:' P" |; k  M' {

1 O: ]1 f+ C* T" T% x+ tUsing Targeted DNA Methylation (TDM), they recruited DNA methyltransferases (DNMTs) to specific loci by introducing methylated DNA complementary to the target.
, G: h7 Y) a0 ?! I$ zConcurrent DNA methylation at tumor suppressor genes RASSF1A and HIC1 in human mesenchymal stem cells (MSCs) resulted in the acquisition of cancer initiating/cancer stem cell features both in vitro and in a xenograft model.
. ]% W, `4 x, l2 C  y$ C4 L* ?The transformed cells had genome-wide changes in DNA methylation and altered p53 function.  / P0 w0 e3 Q% y# t
The tumorigenic phenotype was reversed by treatment with a DNMT inhibitor. . V+ r2 w( N" Z9 y
This is the first demonstration that silencing of particular tumor suppressor genes (TSGs) by aberrant DNA methylation can directly cause somatic stem cells to transform into cancer stem cell (CSC)-like cells.  Hopefully their findings will finally and heritably silence the critics.% Z9 F1 I1 \0 d' t, z
. A, f) y( D( l% }0 }
Determine whether there is a causal link for yourself at Cancer Research, April 2011.
1 O% d2 C4 I: `/ A5 }; G" i* n4 |5 ~4 _: k# k9 p5 \( O
**Find out how to get highly sensitive methylated DNA capture with New England Biolab's EpiMarkTM Methylated DNA Enrichment Kit.4 I+ y( B# G) e# r9 A* Y) U* w3 [

Rank: 2

积分
277 
威望
277  
包包
31  

优秀会员

藤椅
发表于 2011-5-4 16:12 |只看该作者
好文章!!强烈求原文!!!!!谢谢!!!

Rank: 2

积分
155 
威望
155  
包包
105  
板凳
发表于 2011-5-4 16:39 |只看该作者
干细胞之家微信公众号
求原文

Rank: 3Rank: 3

积分
517 
威望
517  
包包
1299  

金话筒 优秀会员

报纸
发表于 2011-5-6 08:34 |只看该作者
反过来说,把癌细胞中激活抑癌基因,是不是应该也可以把癌细胞转化成正常细胞了?
已有 1 人评分威望 包包 收起 理由
细胞海洋 + 2 + 10 欢迎参与讨论

总评分: 威望 + 2  包包 + 10   查看全部评分

Rank: 3Rank: 3

积分
538 
威望
538  
包包
1039  

优秀会员

地板
发表于 2011-5-6 14:32 |只看该作者
,这不错,可以做为一个不错的方法来研究别的,呵呵
附件: 你需要登录才可以下载或查看附件。没有帐号?注册
已有 1 人评分威望 包包 收起 理由
细胞海洋 + 2 + 10 极好资料

总评分: 威望 + 2  包包 + 10   查看全部评分

Rank: 2

积分
106 
威望
106  
包包
932  
7
发表于 2011-5-9 14:09 |只看该作者
谢谢分享# g7 Z) T. l! z- F

Rank: 1

积分
威望
0  
包包
279  
8
发表于 2011-5-12 23:18 |只看该作者
谢谢

Rank: 1

积分
威望
0  
包包
16  
9
发表于 2011-5-30 09:42 |只看该作者
谢谢分享,辛苦了

Rank: 1

积分
威望
0  
包包
16  
10
发表于 2011-5-30 09:44 |只看该作者
谢谢分享,辛苦了
‹ 上一主题|下一主题
你需要登录后才可以回帖 登录 | 注册
验证问答 换一个

Archiver|干细胞之家 ( 吉ICP备2021004615号-3 )

GMT+8, 2024-11-1 06:54

Powered by Discuz! X1.5

© 2001-2010 Comsenz Inc.