Cyclin G2 Dysregulation in human oral cancer
Cyclin G2 Dysregulation in human oral cancer
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DOI：
10.1158/0008-5472.can-04-1926
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发表时间：
2004-12-15
期刊：
影响因子：
11.2
通讯作者：
Wong, DT
中科院分区：
文献类型：
--
作者：
Kim, Y;Shintani, S;Wong, DT
使用表达微阵列，我们以前已经表明，人细胞周期蛋白G2（hCG 2）是显着下调激光捕获显微切割口腔癌上皮。Western分析显示，正常（2/2）口腔角质形成细胞系中可检测到hCG 2蛋白，但在恶性（4/4）口腔角质形成细胞系中检测不到hCG 2蛋白。对口腔癌进行的免疫组化分析显示，正常口腔粘膜（100%，12/12）和69.1%（47/68）的发育不良口腔上皮细胞在细胞核中表达容易检测到的hCG 2。然而，只有11.1%的口腔癌上皮细胞（14/126）显示轻度hCG 2核染色。有趣的是，在112例无细胞核hCG 2的口腔癌中，58例（52%）显示胞浆hCG 2免疫染色，而其他54例（48%）既不显示细胞核也不显示胞浆hCG 2染色。体外功能研究显示，异位恢复hCG 2表达可明显抑制人恶性鳞状细胞癌（SCC 15）细胞的增殖（P < 0.001）和集落形成（P < 2 × 10 - 5），并使细胞G1期细胞数增加，S期细胞数减少（P < 0.01）。此外，在永生化的正常口腔角质形成细胞中，通过基于短干扰RNA的基因沉默稳定下调hCG 2导致细胞生长增强，S期增加，G（2）期显著增加。由于hCG 2被认为是细胞周期进程中的负调节因子，我们的研究结果支持hCG 2失调可能在上皮转化和人类口腔癌发展的早期阶段发挥重要作用。
Using expression microarray, we have previously shown that human cyclin G2 (hCG2) is significantly down-regulated in laser capture microdissected oral cancer epithelia. Western analysis showed detectable hCG2 protein in normal (2 of 2) but not in malignant (4 of 4) oral keratinocyte cell lines. Immunohistochemistry analysis done on oral cancers showed that normal oral mucosa (100%, 12 of 12) and 69.1% (47 of 68) of dysplastic oral epithelia expressed readily detectable hCG2 in the nuclei. However, only 11.1% of oral cancer epithelia (14 of 126) showed mild hCG2 nuclear staining. Interestingly, of the oral cancers devoid of nuclear hCG2 (112 cases), 58 cases (52%) showed cytoplasmic hCG2 immunostaining, whereas the other 54 cases (48%) exhibited neither nuclear nor cytoplasmic hCG2 staining. In vitro functional study by ectopic restoration of hCG2 expression in the human malignant squamous cell carcinoma (SCC) line SCC15 resulted in a significant inhibition of cellular proliferation (P < 0.001) and colony formation (P < 2 x 10(-5)) with increased population of G(1) phase and decreased in S phase (P < 0.01). Furthermore, stable down-regulation of hCG2 by short interference RNA-based gene silencing in immortalized normal oral keratinocytes resulted in enhanced cell growth with increase in S and prominently in G(2) phase. Because hCG2 has been implicated as a negative regulator in cell cycle progression, our results support that hCG2 dysregulation may play an important role in epithelial transformation and the early stages of human oral cancer development.