Gensert JoAnn M, Baranova Oxana V, Weinstein David E, Ratan Rajiv R
The Winifred Masterson Burke/Cornell Medical Research Institute, 785 Mamaroneck Ave., White Plains, NY 10605, USA.
Neurobiol Dis. 2007 Jun;26(3):671-80. doi: 10.1016/j.nbd.2007.03.008. Epub 2007 Mar 28.
Recent advances in cancer cell biology have focused on histone deacetylase inhibitors (HDACi's) because they target pathways critical to the development and progression of disease. In particular, HDACi's can induce expression of epigenetically silenced genes that promote growth arrest, differentiation and cell death. In glioma cells, one such repressed gene is the tetraspanin CD81, which regulates cytostasis in various cell lines and in astrocytes, the major cellular component of gliomas. Our studies show that HDACi's, trichostatin and sodium butyrate, promote growth arrest and differentiation with negligible cell death in glioma cells and induce expression of CD81 and cyclin-dependent kinase inhibitor 1A (p21(CIP/WAF-1)), another regulator of cytostasis in astrocytes. Interference RNA knock-down of CD81 abrogates cytostasis promoted by HDAC inhibition indicating that HDACi-induced CD81 is responsible for growth arrest. Induction of CD81 expression through HDAC inhibition is a novel strategy to promote growth arrest in glioma cells.
癌细胞生物学的最新进展聚焦于组蛋白去乙酰化酶抑制剂（HDACi），因为它们靶向疾病发生和发展的关键途径。特别是，HDACi可诱导表观遗传沉默基因的表达，这些基因促进生长停滞、分化和细胞死亡。在胶质瘤细胞中，一个这样的被抑制基因是四跨膜蛋白CD81，它在各种细胞系和星形胶质细胞（胶质瘤的主要细胞成分）中调节细胞静止。我们的研究表明，HDACi曲古抑菌素和丁酸钠在胶质瘤细胞中促进生长停滞和分化，细胞死亡可忽略不计，并诱导CD81和细胞周期蛋白依赖性激酶抑制剂1A（p21（CIP/WAF-1））的表达，p21（CIP/WAF-1）是星形胶质细胞中另一种细胞静止调节因子。通过干扰RNA敲低CD81可消除HDAC抑制所促进的细胞静止，这表明HDACi诱导的CD81负责生长停滞。通过HDAC抑制诱导CD81表达是促进胶质瘤细胞生长停滞的一种新策略。
