AP-1超家族成员以调节一系列肿瘤发生基因的表达而出名,同时也是治疗上理想的靶位点,但是在人口腔癌中AP-1的机制并不是很清楚.由于口腔癌在印度和东南亚是众多常见癌症之一,因此我们在不同的口腔癌阶段对AP-1家族的蛋白和mRNA进行了表达和激活作用研究.通过Gel shift assay、 western blotting、免疫组化和northern blotting在100个口腔癌新鲜标本中（癌前瘤40、癌瘤50、正常10）分析了AP-1家族(c-Jun, JunB, JunD, c- Fos, FosB, Fra-1and Fra-2)蛋白和mRNA转录本的表达模式和结合活性.在100个口腔癌新鲜标本中（癌前瘤40、癌瘤50、正常10）.在癌组织中发现大部分的AP-1家族的蛋白和mRNA组成性激活.过表达EGFR mRNA, p50:p50/NF-kB同型二聚体和pERK 、c-Fos蛋白发现在口腔癌中AP-1和NF-kappaB信号途径有相互干扰.因此本研究揭示了AP-1超家族蛋白的表达和活性的差异性与口腔癌的严重程度相关,他们与口腔癌的形成有重要关系.

  Trans-activation and expression patterns of jun and fos / AP-1 super-family proteins in human oral cancer.
Mishra A, Bharti AC, Saluja D, Das BC.
  Division of Molecular Oncology, Institute of Cytology and Preventive Oncology, (ICMR), I - 7, Sector -39, Noida - 201301, INDIA.
  Transcription factor Activator Protein-1 (AP-1) superfamily is known to modulate expression of array of genes during development of many cancers and considered as an important target for modern therapeutics. But the role of AP-1 during development of human oral cancers is still poorly understood. Since oral cancer is one of the most common cancers in India and south-east Asia we studied the activation and expression pattern of AP-1 family of proteins and mRNA in different stages of oral carcinogenesis. Gel shift assay, western blotting, immunohistochemistry and northern blotting have been employed to assess the binding activity and expression pattern of AP-1 family (c-Jun, JunB, JunD, c- Fos, FosB, Fra-1and Fra-2) proteins and mRNA transcripts in a total of 100 fresh oral tissue specimens comprising precancer (n=40), cancer (n=50) and healthy control (n=10). Constitutive activation of AP-1 with concomitant upregulated expression of majority of AP-1 family of proteins and mRNA was observed in cancer cases. Interestingly, almost all precancerous cases showed JunD homodimers while c-Fos/JunD was the most prevalent complex found in cancer tissues. The overexpression of EGFR mRNA, p50:p50/NF-kB homodimer formation, together with over expression of pERK and c-Fos proteins in the present study suggests an interesting cross talk between AP-1 and NF-kappaB pathways in oral cancers. Thus, this study demonstrates differential expression and activation of AP-1 super-family proteins in relation to severity of lesion and their crucial role in human oral carcinogenesis. (c) 2009 UICC.
1: Int J Cancer. 2009 Aug 3. [Epub ahead of print.

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