Expression and mutation analysis of heterogeneous nuclear ribonucleoprotein G in human oral cancer.

Expression and mutation analysis of heterogeneous nuclear ribonucleoprotein G in human oral cancer.
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DOI:
10.1016/j.oraloncology.2011.07.012
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发表时间:
2011-11
期刊:
影响因子:
4.8
通讯作者:
Park, No-Hee
Park, No-Hee
中科院分区:
医学2区
文献类型:
--
作者:
Shin, Ki-Hyuk;Kim, Reuben H.;Yu, Bo;Kang, Mo K.;Elashoff, David;Christensen, Russell;Pucar, Ana;Park, No-Hee

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我们以前报道过野生型hnRNP G在缺乏hnRNP G的人口腔鳞状细胞癌(HOSCC)细胞系中表现出肿瘤抑制活性。wthnRNP G可明显抑制HOSCC细胞的增殖能力、贴壁依赖性和体内致瘤性,并显著增强其DNA修复能力。为了进一步了解hnRNP G基因在口腔癌发生发展中的作用,本研究对hnRNP G基因在正常口腔组织、癌前病变组织和口腔癌组织中的表达进行了研究。为探讨hnRNP G表达水平与口腔癌发生发展的关系,我们采用免疫组化方法检测了正常口腔组织、癌前病变组织和口腔癌组织中hnRNP G的表达。此外,我们检查了整个编码区的hnRNP G从选定的样品,以了解基因表达的改变的原因。hnRNP G在80%的癌前-异型增生和恶性口腔上皮组织中表达明显减少或完全消失,而100%的正常和90%的增生非异型增生上皮显示高水平的hnRNP G在基底细胞层的细胞核中。大约80%缺乏hnRNP G表达的HOSCC显示hnRNP G的遗传改变,即,点突变和外显子缺失。提示口腔癌发生过程中hnRNP G基因的改变和表达异常可能是口腔癌早期诊断的有用指标。
We previously reported that wild type (wt) hnRNP G exhibited tumor suppressive activity in human oral squamous cell carcinoma (HOSCC) cell lines lacking hnRNP G. Wt hnRNP G markedly inhibited the proliferation capacity, anchorage independency and in vivo tumorigencity of HOSCC cells and notably enhanced the DNA repair capabilities of these cells. In the present study, we studied the genetic and expression states of hnRNP G in normal, premalignant and malignant human oral tissues to further understand the relationship between the hnRNP G alterations and the development of human oral cancer. To correlate the cancer development and the level of hnRNP G expression, we performed an immunohistochemistry staining of hnRNP G in normal, premalignant and malignant human oral tissues. Moreover, we examined the entire coding regions of hnRNP G from selected samples to understand the cause of the alterations of the gene expression. The expression of hnRNP G was notably decreased or completely abolished in 80% of premalignant-dysplastic and malignant oral epithelial tissues, whereas 100% of normal and 90% of hyperplastic non-dysplastic epithelium showed high level of hnRNP G in the nucleus of the basal cell layers. Approximately 80% of HOSCC lacking the expression of hnRNP G showed genetic alteration in hnRNP G, i.e., point mutation and exonic deletion. This study suggest that genetic alterations and aberrant expression of hnRNP G occurring during oral carcinogenesis might be useful markers for the early detection of human oral cancer.
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