癌细胞重编程——卵母成分可重写肿瘤的表观遗传信息

sunsong7

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Epigenetic reprogramming of breast cancer cells with oocyte extracts

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4 u- A$ K0 Z( l) a1 NCinzia Allegrucci1,2*, Michael D Rushton1, James E Dixon1, Virginie Sottile1,3, Mansi Shah2, Rajendra Kumari4, Sue Watson4, Ramiro Alberio1,5 and Andrew D Johnson1* 3 S, F* }2 J' D9 J2 T0 Z- B
Molecular Cancer 2011, 10:7 doi:10.1186/1476-4598-10-7   Published: 13 January 2011
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Background - Y1 q8 _" R  F) Y6 b
Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis.
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Results
! J3 y% Q! \- O1 I6 R! MWe show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts. 6 u, o: \- Q4 q& R" e" E' R& Q
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Conclusions " D6 L% y' w2 C! G
This study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.
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http://www.molecular-cancer.com/content/10/1/7/abstract

fgh1124

文章已看过，亮点二个：1. oocyte extracts 诱导reprogramming；" K: x  f9 f. i3 a4 @2 C$ Z& m
2. 癌细胞可以被诱导epigentic reprogramming;2 i/ k% S7 X2 J" [; n
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问题：
+ U# A, \9 e: ~3 o7 t; K* ?1. oocyte extracts 诱导reprogramming 是不是首次提出，请牛人提供文献？9 B1 _! x0 a3 l9 N$ T7 V
2. epigentic reprogramming 距离cell reprogramming 还有多远？
" |" Z+ u+ r# [3. 有没有可能诱导 cancer cell reprogramming？8 Y% F% Q" ~' w! b" A( A9 z4 w
谢谢，牛人解答！

sunsong7

回复 fgh1124 的帖子
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$ C: ~6 F# w, p1 u: f& `( j. y【相关讨论】重编程技术革命——niche reprogramming http://www.stemcell8.cn/thread-40755-1-1.html2 ^1 |6 k: p2 }6 c4 N

always_wp

hormone008

文章看过了，我在考虑一个问题，如此有新意的文章为什么只发了Molecular Cancer杂志，此杂志仅有4.6分。5 S! j/ |! ?: s9 H
我想作者肯定投过高分杂志，当然被高分杂志拒稿，那么，这些杂志的编委是出于什么考虑拒稿呢？此文章的缺陷在哪里呢？
1 O) r8 L+ v& J我再考虑，有人给我解答一下吗？
7 C$ n/ d7 V7 t+ T谢谢
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hormone008

回复 fgh1124 的帖子
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问题1; u% o% T' N; S2 B* K2 D8 E. y
肯定不是首次提出，在核移植导致的克隆动物就是其理论的最好实践证明
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$ W2 {( ]) F  W" Z' }, C问题2  s0 a: Q6 A3 O3 ~8 {6 J6 I
无法回答3 L0 d4 t3 B) u" V

7 J: q: [$ S6 W; r' N问题3
" R9 o7 r, R+ E1 D- C: {( N9 c; F有可能，我非常赞同此观点。在血癌里，就有最好的例子，全反式维甲酸诱导分化治疗。. A" \0 m2 y. J0 Z9 ]

& G" r# V* L+ r8 ]* J以上为个人观点，希望抛砖引玉，引出牛人的回答！7 ^8 H) I5 o6 e- n

sunsong7

回复 hormone008 的帖子
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& ]; d* t# f; |- ?类似的研究早有一些，当下大家都在忙着追杀癌细胞，将肿瘤细胞重编程的尝试尚不被主流专家看好；

xiangchou812

如果是这样的话，那么是不是那些由于表观遗传改变而引发的肿瘤细胞就可以经过SCNT，生下正常的后代呢？如果能成功的话，肯定是nature级的文章了

sunsong7

回复 xiangchou812 的帖子
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很好的的想法，, _+ a5 W+ i) J8 u9 ~! f

; N7 I% J$ L5 m; R- j3 A老狼认为，肿瘤来自于以细胞自发重编程，既然可以把干细胞编程为肿瘤，逆编程的路径也应该存在，有证据表明全能性细胞（ESC，iPSC, cancer？）在胚胎性微环境中倾向于有序分化，在非胚胎性微环境中倾向于形成肿瘤。
- y( d0 n# B: I6 A肿瘤问题不出在狼来了而是狼跑了，不是狼变坏了而是狼圈坏了，解决出路在于对细胞的微环境干预而不是把只盯住遗传物质变异；

xiangchou812

回复 sunsong7 的帖子
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我对肿瘤方面了解不多，不过听过别人的报告，说是现在对肿瘤的产生的原因还存在不同的假说。不知道肿瘤细胞的遗传物质有没有发生改变，也就是说是不是由于遗传物质的突变引物肿瘤的？请多指教。