Neoplasma. 2014;61(4):468-75. doi: 10.4149/neo_2014_058.
The inhibitor of growth 2 (ING2) is a member of lNG family, involved in cell cycle regulation, DNA repair, apoptosis and senescence, and participating in chromatin remodeling and transcriptional regulation by histone modification. Recent researches suggest ING2 plays roles in carcinogenesis both as tumor suppressor gene and ongocene depending on tumor types and cell status. Here, we investigated the status of ING2 in a series of 64 Chinese non-small cell lung cancer (NSCLC)patients using immunohistochemistry (IHC) and confirmed the results with Western blotting. RT-PCR results revealed the expression level of ING2 was consistent with mRNA level. The IHC results showed that ING2 protein expression was significantly decreased in NSCLC samples compared with normal lung tissues (P<O.OS). ING2 expression was lost in 32.8%(21/64) NSCLC tissues, which was more frequently in adenocarcinoma (ADK) than in squamous cell carcinoma (SCC), 45.8%(11124) and 26.3% (10/38), respectively. We also found ING2 translocation from the nucleus to the cytoplasm, which may bea critical event for carcinogenesis. And the status of ING2 in SCC was significantly associated with lymph node metastasis status and TNM stage. After sequencing ING2 gene, we found no heterozygosity or mutation. Taken together, these results indicated that the aberrantly expression of ING2 may contribute to NSCLC tumorigenesis.
抑生长因子 2(ING2)是 ING 家族的一员,参与细胞周期调控、DNA 修复、凋亡和衰老,并通过组蛋白修饰参与染色质重塑和转录调控。最近的研究表明,ING2 在肿瘤发生中既作为抑癌基因,也作为癌基因发挥作用,这取决于肿瘤类型和细胞状态。在这里,我们使用免疫组织化学(IHC)方法对 64 例中国非小细胞肺癌(NSCLC)患者进行了 ING2 状态研究,并通过 Western blotting 对结果进行了验证。RT-PCR 结果显示 ING2 的表达水平与 mRNA 水平一致。IHC 结果显示,与正常肺组织相比,NSCLC 样本中 ING2 蛋白表达明显降低(P<0.05)。在 64 例 NSCLC 组织中,ING2 表达缺失率为 32.8%(21/64),在腺癌(ADK)中比在鳞癌(SCC)中更常见,分别为 45.8%(11/24)和 26.3%(10/38)。我们还发现 ING2 从核内转移到细胞质,这可能是致癌的关键事件。并且 SCC 中 ING2 的状态与淋巴结转移状态和 TNM 分期显著相关。对 ING2 基因进行测序后,我们没有发现杂合性或突变。综上所述,这些结果表明 ING2 的异常表达可能导致 NSCLC 的发生。