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Cell Death Differ:前列腺癌中DNA甲基化是上皮细胞异常分化和增生的结果

  1. 前列腺癌药物

来源:生物谷 2014-01-27 20:25

2014年1月27日讯 /生物谷BIOON/--也许治疗前列腺癌的新开发的药物可能并不能针对疾病的根本原因,治疗疾病,根据发表在Cell Death & Differentiation杂志上一项最新研究证实。

近日,York大学科学家发现了​​一个名为“甲基化”的过程(以前被认为能推动癌症的发展),实际上发生在已经癌变的细胞中,即甲基化发生前细胞已经癌变。这一发现意味着旨在扭转这个甲基化过程的疗法未必能有效对抗癌症干细胞,成功治疗癌症。

主要研究人员Pellacani博士说:要发展成为癌症,健康细胞中的某些蛋白质需要被关闭。有时候,这是由甲基化引发的。前列腺癌细胞和非癌细胞的甲基化过程有明显的差异,先前有研究提示此过程可以驱动癌症的进展,而这一过程通过使用特定药物逆转,但新的研究已经表明,这可能并非如此。

前列腺癌是由两种类型的细胞组成:罕见基底细胞(包括干细胞),来源于已经形成肿瘤组织中,以及管腔细胞(形成肿瘤块)。研究小组发现,基础基底细胞向管腔细胞的演变(一种叫做分化过程)与甲基化差异密切相关,提示前列腺癌细胞中的甲基化可能并不是癌症的主要驱动力。(生物谷Bioon.com)

 

DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation

D Pellacani, D Kestoras, A P Droop, F M Frame, P A Berry, M G Lawrence, M J Stower, M S Simms, V M Mann, A T Collins, G P Risbridger and N J Maitland

Prostate cancer (CaP) is mostly composed of luminal-like differentiated cells, but contains a small subpopulation of basal cells (including stem-like cells), which can proliferate and differentiate into luminal-like cells. In cancers, CpG island hypermethylation has been associated with gene downregulation, but the causal relationship between the two phenomena is still debated. Here we clarify the origin and function of CpG island hypermethylation in CaP, in the context of a cancer cell hierarchy and epithelial differentiation, by analysis of separated basal and luminal cells from cancers. For a set of genes (including GSTP1) that are hypermethylated in CaP, gene downregulation is the result of cell differentiation and is not cancer specific. Hypermethylation is however seen in more differentiated cancer cells and is promoted by hyperproliferation. These genes are maintained as actively expressed and methylation-free in undifferentiated CaP cells, and their hypermethylation is not essential for either tumour development or expansion. We present evidence for the causes and the dynamics of CpG island hypermethylation in CaP, showing that, for a specific set of genes, promoter methylation is downstream of gene downregulation and is not a driver of gene repression, while gene repression is a result of tissue-specific differentiation.

 

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