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Cell Journal، جلد ۱۶، شماره Suppl ۱، صفحات ۱۹-۱۹
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عنوان انگلیسی Is-19: Unexpected Results of Prolonged Ezh2 Inhibition in An In Vivo Model for Glioblastoma
چکیده انگلیسی مقاله Repressive Polycomb-group (Pc-G) protein complexes and the counteracting Trithorax-group (Trx-G) of nucleosome remodeling factors are involved in the dynamic maintenance of proper gene expression patterns during development, acting at the level of chromatin structure. As such, they are important controllers of cell fate and differentiation. When deregulated, these master switches of gene expression are strongly implicated in formation of a diverse set of cancers. Examples are the Pc-G gene Bmi1 and Ezh2 which are overexpressed in many cancers including Glioblastoma. However, recently Ezh2 has also been found to be mutated/inactivated in other forms of cancer, suggesting a highly context-dependent role as oncogene or tumor suppressor. An outstanding question is how to identify among the many Pc-G bound genes the cancer-relevant ones. hereto we have recently combined stringent ChIP-seq with custom shRNAi library screening in in vivo models for glioblastoma. As Ezh2 is associated with poor prognosis and metastasis in many cancer settings there is an increasing interest for development of selective Ezh2 inhibitors as potential new ways for epigenetic cancer therapy. We have developed conditional shRNAi inhibition in mouse models for aggressive Glioma to study the effects of Ezh2 inhibition on tumor initiation and maintenance. Whereas initial tumor regression upon Ezh2 inhibition was observed in vivo, prolonged Ezh2 inhibition caused unexpected profound changes in tumor plasticity, differentiation status with important consequences for tumor progression and treatment options, which will be discussed.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/313
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