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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, b1 |3 z$ k7 B3 r8 E0 n- l3 @Cinzia Allegrucci1,2*, Michael D Rushton1, James E Dixon1, Virginie Sottile1,3, Mansi Shah2, Rajendra Kumari4, Sue Watson4, Ramiro Alberio1,5 and Andrew D Johnson1*
6 Q' j  Q" C2 h; E! f, |Molecular Cancer 2011, 10:7 doi:10.1186/1476-4598-10-7   Published: 13 January 2011
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  s) d$ f7 [0 I/ V/ RBackground
1 f3 X- w, Y: r' kBreast 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. 7 ~' n1 i; S8 X3 O
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Results
3 N9 t5 v+ `; i! w% ~We 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. ( c- C+ X. b8 P$ J) }9 T" v

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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.  v# T; V( \) ], V9 N5 u
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http://www.molecular-cancer.com/content/10/1/7/abstract

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回复 fgh1124 的帖子
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【相关讨论】重编程技术革命——niche reprogramming http://www.stemcell8.cn/thread-40755-1-1.html& S. q# y. r+ a; x/ K1 A6 E

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回复 hormone008 的帖子1 A1 T8 ^5 D; L# q
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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；

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回复 xiangchou812 的帖子
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2 _- m8 I6 b& }4 B( l) f6 N很好的的想法，
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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。- R  u2 H% F6 L. z$ k/ k
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；

sunsong7

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回复 xiangchou812 的帖子
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体细胞的基因组都是相同的，在细胞分化及异常分化情况下会发生DNA甲基化或去甲基化等表观遗传修饰，相当于基因的选择性“开”或“合”，如果原癌基因被异常激活或抑癌基因被关闭就有可能产生肿瘤，肿瘤细胞产生后由于肿瘤代谢异常，一些肿瘤相关蛋白基因持续转录，造成大量基因突变，并发生核型异常、染色体畸变等等遗传物质的突变....
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老狼认为遗传物质的突变与肿瘤发生的没有任何关系，仅仅是肿瘤细胞产生以后非受控活动的表象。
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6 y2 w) c; y+ {8 Q肿瘤是一种细胞分化疾病，细胞分化方向完全由细胞微环境决定的，而微环境“授权”细胞质“掌控”细胞命运，细胞质把“执行权”交给了miRNA....DNA在整个过程中的作用仅仅是充当堆放遗传信息的“库房”，没有直接参与其他任何生理活动，肿瘤遗传物质的突变是“果”而非“因”；
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事实上，近几十年来全球科学家几乎都致力于肿瘤遗传物质和分子生物学研究，花掉数千亿美元无功而返....( R3 J# g7 t9 L# G5 L: G/ W
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