Aberrant expression of histone deacetylase 6 in oral squamous cell carcinoma.
Aberrant expression of histone deacetylase 6 in oral squamous cell carcinoma.
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DOI：
10.3892/ijo.29.1.117
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发表时间：
2006-07
影响因子：
5.2
通讯作者：
Takumi Sakuma;K. Uzawa;Takeshi Onda;M. Shiiba;H. Yokoe;T. Shibahara;H. Tanzawa
中科院分区：
文献类型：
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作者：
Takumi Sakuma;K. Uzawa;Takeshi Onda;M. Shiiba;H. Yokoe;T. Shibahara;H. Tanzawa
组蛋白的修饰可以改变染色质的结构和功能。组蛋白乙酰化是一个由组蛋白乙酰转移酶和组蛋白脱乙酰酶(HDAC)控制的可逆过程。HDAC6是HDAC家族的一个亚型，它能使α-微管蛋白去乙酰化，增加细胞的运动性。我们研究了HDAC6在口腔鳞状细胞癌(OSCC)来源的细胞系和人原代OSCC中的表达水平，以阐明HDAC6在口腔鳞癌中的潜在作用。应用实时定量逆转录聚合酶链式反应和Western blotts对9个口腔鳞癌来源的细胞系和正常口腔角质形成细胞(NOK)进行检测，发现HDAC6mRNA和蛋白在所有细胞系中的表达普遍高于NOK。免疫荧光分析检测到口腔鳞癌细胞系胞浆内有HDAC6蛋白表达。与口腔鳞癌细胞系相似，HDAC6在原发灶中的基因表达水平(74%)和蛋白水平(51%)均明显上调。在分析的临床变量中，临床肿瘤分期与HDAC6的表达状态有关。分析表明，早期(I、II期)和晚期(III、IV期)肿瘤组织中HDAC6的表达水平有显著差异(P=0.014)。这些结果表明，HDAC6的表达可能与肿瘤的侵袭性有关，并为新的治疗方案的制定提供了线索。
The structure and function of chromatin can be altered by modifications to histone. Histone acetylation is a reversible process governed by histone acetyltransferases and histone deacetylases (HDACs). HDAC6 is a subtype of the HDAC family that deacetylates alpha-tubulin and increases cell motility. We investigated the expression levels of HDAC6 mRNA and protein expression in oral squamous cell carcinoma (OSCC)-derived cell lines and human primary OSCCs to elucidate the potential involvement of HDAC6 in OSCC. Using quantitative real-time reverse transcription polymerase chain reaction and Western blots on nine OSCC-derived cell lines and normal oral keratinocytes (NOKs), HDAC6 mRNA and protein expression were commonly up-regulated in all cell lines compared with the NOKs. Immunofluorescence analysis detected HDAC6 protein in the cytoplasm of OSCC cell lines. Similar to OSCC cell lines, high frequencies of HDAC6 up-regulation were evident in both mRNA (74%) and protein (51%) levels of primary tumors. Among the clinical variables analyzed, the clinical tumor stage was found to be associated with the HDAC6 expression states. The analysis indicated a significant difference in the HDAC6 expression level between the early stage (stage I and II) and advanced-stage (stage III and IV) tumors (P=0.014). These results suggest that HDAC6 expression may be correlated with tumor aggressiveness and offer clues to the planning of new treatments.