Department of Otolaryngology-Head and Neck Surgery, the Johns Hopkins Medical Institutions, Baltimore, MD, USA.
PLoS One. 2012;7(11):e48582. doi: 10.1371/journal.pone.0048582. Epub 2012 Nov 7.
Salivary gland adenoid cystic carcinoma (ACC) is a rare cancer, accounting for only 1% of all head and neck malignancies. ACC is well known for perineural invasion and distant metastasis, but its underlying molecular mechanisms of carcinogenesis are still unclear.
Here, we show that a novel oncogenic candidate, suprabasin (SBSN), plays important roles in maintaining the anchorage-independent and anchorage-dependent cell proliferation in ACC by using SBSN shRNA stably transfected ACC cell line clones. SBSN is also important in maintaining the invasive/metastatic capability in ACC by Matrigel invasion assay. More interestingly, SBSN transcription is significantly upregulated by DNA demethylation induced by 5-aza-2'-deoxycytidine plus trichostatin A treatment and the DNA methylation levels of the SBSN CpG island located in the second intron were validated to be significantly hypomethylated in primary ACC samples versus normal salivary gland tissues.
CONCLUSIONS/SIGNIFICANCE: Taken together, these results support SBSN as novel oncogene candidate in ACC, and the methylation changes could be a promising biomarker for ACC.
唾液腺腺样囊性癌(ACC)是一种罕见的癌症,仅占头颈部恶性肿瘤的 1%。ACC 以神经周围侵犯和远处转移而闻名,但其潜在的致癌分子机制仍不清楚。
在这里,我们通过使用 SBSN shRNA 稳定转染的 ACC 细胞系克隆,显示了一种新的致癌候选物——超基底蛋白(SBSN)在维持 ACC 中的锚定独立和锚定依赖性细胞增殖方面发挥着重要作用。SBSN 在 ACC 的侵袭/转移能力中也很重要,通过 Matrigel 侵袭实验证实。更有趣的是,5-氮杂-2'-脱氧胞苷加曲古抑菌素 A 处理诱导的 DNA 去甲基化显著上调 SBSN 转录,并且在原发性 ACC 样本中,SBSN 第二内含子中 CpG 岛的 DNA 甲基化水平明显低于正常唾液腺组织。
结论/意义:综上所述,这些结果支持 SBSN 作为 ACC 中的新型致癌基因候选物,并且甲基化变化可能是 ACC 的有前途的生物标志物。