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[癌症发生中的染色质表观遗传修饰]

[Chromatin epigenetic modifications in cancer generation].

作者信息

Arenas-Huertero Francisco, Recillas-Targa Félix

机构信息

Depto. Oncología, Hospital Infantil de México Federico Gómez-SS, Avenida Dr. Márquez 162, Colonia de los Doctores, 06720, México, D.F.

出版信息

Gac Med Mex. 2002 Nov-Dec;138(6):547-55.

Abstract

Chromatin is more than a simple staining structure inside the nucleus. It represents a level of organization that regulates transcriptional activation in eukaryotic genes; this may be through epigenetic modifications such as DNA methylation, histone acetylation, deacetylation and methylation, and chromatin remodeling complexes. Chromatin can have a direct impact on regulating gene expression. Several human diseases arise from alterations of epigenetic regulation, causing change in chromatin structure: cancer is not the exception. The expression of tumor suppressor genes can be epigenetically silenced by DNA methylation of their promotor regions. In other cases such as leukemias, imbalance of histone acetylation and deacetylation can be a determinant event to induce a leukemic phenotype. Finally, improper imprinting can also be associated with neoplastic transformation as in Wilms tumors and sporadic colon cancer. All this evidence supports our particular attention to the study of chromatin structure in cancer. The use of compounds that modify chromatin to improve effects of radio- and chemotherapy will open new horizons in what we call Chromatin Therapy in cancer.

摘要

染色质不仅仅是细胞核内一种简单的染色结构。它代表了一种调控真核基因转录激活的组织水平;这可能是通过表观遗传修饰,如DNA甲基化、组蛋白乙酰化、去乙酰化和甲基化,以及染色质重塑复合体来实现的。染色质能够对基因表达调控产生直接影响。几种人类疾病源于表观遗传调控的改变,导致染色质结构发生变化:癌症也不例外。肿瘤抑制基因的表达可因其启动子区域的DNA甲基化而在表观遗传上被沉默。在其他情况下,如白血病,组蛋白乙酰化和去乙酰化的失衡可能是诱导白血病表型的决定性事件。最后,印记异常也可能与肿瘤转化有关,如在肾母细胞瘤和散发性结肠癌中。所有这些证据都支持我们对癌症中染色质结构研究给予特别关注。使用能够修饰染色质以提高放疗和化疗效果的化合物,将为我们所谓的癌症染色质治疗开辟新的前景。

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