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本帖最后由 细胞海洋 于 2011-5-6 15:18 编辑 * n0 E, z6 n" F i2 [% {2 m) t
2 H/ A* s: [$ t& t( {7 UTargeted methylation of two tumor suppressor genes is sufficient to transform mesenchymal stem cells into cancer stem/initiating cells
# o( g6 a- x1 {( [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）
& M" V; [0 p; HCancer research http://cancerres.aacrjournals.or ... AN-10-3418.abstract& Z4 F$ ] ?9 K# H8 [+ ]
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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
" Q) z4 k7 F* T+ Author Affiliations
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1Department of Life Science, National Chung Cheng University
8 y" {& A6 `+ ]0 A2Hematology and Oncology, Chang Gung Memorial Hospital
- \" \2 p! Y# \. q- X9 e/ w/ B6 t3Pathology, ChangHua Christian Hospital
/ f! P) [ n+ ?+ F4Department of Pathology, Changhua Christian Hospital
$ V, n+ N! M8 n M5Biomedical Informatics, The Ohio State University
( `( O: p: _1 w! e" |6Department of Physiology, National Cheng Kung University
; F& \7 {2 T6 l) W3 z7Graduate Institute of Basic Medical Sciences, Chang-Gung University 9 [4 Y7 H# |8 s
8Molecular Medicine Research Center, Chang Gung University 4 b$ m! ~4 w* I
9National Cheng-Kung University Medical College, Institute of Molecular medicine
$ \) n r0 @" }3 n6 W, p10Department of Internal Medicine, China Medical University Peikang Hospital
5 F# C1 K; t4 Q& ~+ c0 y11Cellular and Integrative Physiology, Indiana University : B& x* m7 k# Y+ K5 q) B# j I
12Human Cancer Genetics, MVIMG Dept, The Ohio State University ' g2 ^. U. |" B5 m
13Life Science, National Chung Cheng University
# k& C, B* k6 C0 d/ c6 w* V4 a14Chung-Cheng University 0 O* x1 R f, z3 y
Corresponding Author:2 Z" P/ u0 B* N, f0 U
Shu-Huei Hsiao, Life Science, National Chung Cheng University, 168 University Road, Min Hsiung, Chia-Yi, 621, Taiwan bioshh@ccu.edu.tw 4 _1 X2 s' E8 i! h6 ?" Y& I$ h
Abstract2 Y0 ~# C. }" T8 n0 @! ]
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. 2 W8 ]- K+ L' Y; o/ d$ e4 m3 Q
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Received September 17, 2010. $ ~, |9 c/ Z) B
Revision received March 27, 2011. - t t1 ^) d4 H6 @3 z$ z7 D' i
Accepted April 18, 2011. 9 c* S5 }! i: n J) c
Copyright © 2011, American Association for Cancer Research.
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! G& f1 `# ?/ A' N6楼原文 感谢apengforever 提供 |
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发表于 2011-5-4 10:30
发表于 2011-6-17 12:01
