Genetic or epigenetic silencing of low density lipoprotein receptor-related protein 1B expression in oral squamous cell carcinoma
Genetic or epigenetic silencing of low density lipoprotein receptor-related protein 1B expression in oral squamous cell carcinoma
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DOI：
10.1111/j.1349-7006.2006.00283.x
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发表时间：
2006-10-01
期刊：
影响因子：
5.7
通讯作者：
Imoto, Issei
中科院分区：
文献类型：
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作者：
Nakagawa, Takayuki;Pimkhaokham, Atiphan;Imoto, Issei
之前，我们已经报道了LRP1B在食管鳞状细胞癌中通过遗传和表观遗传机制的表达沉默。由于相同的事件可能涉及OSCC的发生/进展，我们检查了该基因CpG岛的基因内纯合缺失、表达水平和甲基化状态。18株OSCC细胞系中仅有1株（5.6%）检测到纯合子缺失，17株OSCC细胞系中有8株（47.1%）未检测到LRP1B mRNA表达沉默。在OSCC细胞系中，mRNA表达与LRP1B CpG岛甲基化状态明显呈负相关，5-aza-dCyd处理后，LRP1B mRNA表达恢复。在原发性OSCC中也观察到频繁的LRP1B启动子甲基化。综上所述，提示在OSCC中，LRP1B频繁失活主要通过表观遗传机制发生，可能在口腔肿瘤发生中发挥重要作用。
Previously, we have reported frequent silencing of the expression of LRP1B by genetic and epigenetic mechanisms in esophageal squamous cell carcinoma. As the same events might be involved in the development/progression of OSCC, we examined intragenic homozygous deletions, expression levels, and methylation status in the CpG island of this gene. Homozygous deletion was detected in only 1 of 18 (5.6%) OSCC lines, whereas the expression of LRP1B mRNA was silenced in 8 of 17 (47.1%) OSCC lines without homozygous deletion. An inverse correlation between mRNA expression and methylation status of the LRP1B CpG island was clearly observed in OSCC lines, and LRP1B mRNA expression was restored by treatment with 5-aza-dCyd. Frequent methylation of the LRP1B promoter was also observed in primary OSCC. Taken together, the results suggested that frequent inactivation of LRP1B mainly occurs by means of epigenetic mechanisms in OSCC, which might play an important role in oral tumorigenesis.