Over-expression of 14-3-3zeta is an early event in oral cancer.
Over-expression of 14-3-3zeta is an early event in oral cancer.
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14-3-3zeta的过表达是口腔癌的早期事件。
DOI：
10.1186/1471-2407-7-169
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发表时间：
2007-09-02
期刊：
影响因子：
3.8
通讯作者：
Ralhan R
中科院分区：
文献类型：
--
作者：
Matta A;Bahadur S;Duggal R;Gupta SD;Ralhan R
14-3-3蛋白在人类癌症中的功能和临床意义在很大程度上仍未确定。早些时候，我们已经报道了14-3-3ζ基因在口腔鳞状细胞癌中的差异表达。采用免疫组织化学方法检测14-3-3-ζ蛋白在口腔癌前病变、口腔鳞癌和正常口腔组织中的表达，并用免疫印迹法证实14-3-3蛋白在口腔肿瘤发生中的作用。免疫共沉淀法检测其与核因子κB、β-连环蛋白和Bcl2的相关性。69%(61/89)的口腔鳞状细胞癌和79%(95/120)的口腔鳞癌组织中14-3-3ζ蛋白呈强阳性表达。免疫组织化学显示14-3-3ζ蛋白在正常黏膜、口腔黏膜样变和口腔鳞状细胞癌中的表达显著增加(P<0.001)。14-3-3ζ蛋白在口腔鳞癌中的表达早在口腔鳞癌组织中就明显升高(p=0.009)，在中、重度不典型增生组织中表达进一步增强，并持续在口腔鳞癌中。这些发现通过Western blotting得到了验证。免疫共沉淀法证实14-3-3ζ蛋白与核因子κB、β-连环蛋白和Bcl2结合，提示其参与细胞信号转导，导致口腔癌细胞增殖。我们的研究结果表明，14-3-3ζ的过度表达是口腔肿瘤发生的早期事件，可能在口腔肿瘤的发生发展中起重要作用。因此，14-3-3ζ可能成为设计口腔癌新疗法的重要分子靶点。
The functional and clinical significance of 14-3-3 proteins in human cancers remain largely undetermined. Earlier, we have reported differential expression of 14-3-3ζ mRNA in oral squamous cell carcinoma (OSCC) by differential display. The clinical relevance of 14-3-3ζ protein in oral tumorigenesis was determined by immunohistochemistry in paraffin embedded sections of oral pre-malignant lesions (OPLs), OSCCs and histologically normal oral tissues and corroborated by Western Blotting. Co-immunoprecipitation assays were carried out to determine its association with NFκB, β-catenin and Bcl-2. Intense immunostaining of 14-3-3ζ protein was observed in 61/89 (69%) OPLs and 95/120 (79%) OSCCs. Immunohistochemistry showed significant increase in expression of 14-3-3ζ protein from normal mucosa to OPLs to OSCCs (ptrend < 0.001). Significant increase in expression of 14-3-3ζ protein was observed as early as in hyperplasia (p = 0.009), with further elevation in moderate and severe dysplasia, that was sustained in OSCCs. These findings were validated by Western blotting. Using Co-immunoprecipitation, we demonstrated that 14-3-3ζ protein binds to NFκB, β-catenin and Bcl-2, suggesting its involvement in cellular signaling, leading to proliferation of oral cancer cells. Our findings suggest that over-expression of 14-3-3ζ is an early event in oral tumorigenesis and may have an important role in its development and progression. Thus, 14-3-3ζ may serve as an important molecular target for designing novel therapy for oral cancer.
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DOI：
10.1073/pnas.96.4.1603
发表时间：
1999-02-16
影响因子：
11.1
作者：
Mann, B;Gelos, M;Hanski, C
通讯作者：
Hanski, C
影响因子：
4
作者：
Aguilera, Cristina;Fernandez-Majada, Vanessa;Espinosa, Lluis
通讯作者：
Espinosa, Lluis
影响因子：
4.8
作者：
Li, XF;Song, S;Kao, HY
通讯作者：
Kao, HY
影响因子：
4.5
作者：
Sharma, Chhavi;Kaur, Jatinder;Ralhan, Ranju
通讯作者：
Ralhan, Ranju
影响因子：
5.3
作者：
Powell, DW;Rane, MJ;McLeish, KR
通讯作者：
McLeish, KR