Iamaroon Anak, Pattamapun Kassara, Piboonniyom Siribang-On
Department of Odontology and Oral Pathology, Faculty of Dentistry, Chiang Mai University, Thailand.
J Oral Sci. 2006 Sep;48(3):105-9. doi: 10.2334/josnusd.48.105.
Although carcinogenesis of oral squamous cell carcinoma (OSCC) has been studied by many investigators in the past decade, the available evidence about its molecular mechanism is inconclusive. The objective of the present study was to compare expression of Smad4, a signaling molecule of the transforming growth factor beta (TGF-beta) pathway, between OSCC and normal oral mucosa. We assayed expression of Smad4 in OSCC and normal oral mucosa by performing immunohistochemistry using paraffin-embedded tissue samples. We also compared expression of Smad4 protein between OSCC lines and normal oral keratinocytes, using Western blot analysis. Smad4 expression was observed in only 60% of OSCC tissue samples, whereas it was observed in 82% of normal oral mucosa samples. Reduced Smad4 expression was clearly observed in all OSCC lines, compared with normal oral keratinocytes. These findings suggest that aberration of the TGF-beta pathway, as indicated by a reduction or absence of Smad4 expression, promotes carcinogenesis of OSCC.
尽管在过去十年中许多研究人员对口腔鳞状细胞癌(OSCC)的致癌作用进行了研究,但关于其分子机制的现有证据尚无定论。本研究的目的是比较转化生长因子β(TGF-β)信号通路的信号分子Smad4在口腔鳞状细胞癌和正常口腔黏膜中的表达情况。我们通过使用石蜡包埋组织样本进行免疫组织化学分析,检测了Smad4在口腔鳞状细胞癌和正常口腔黏膜中的表达。我们还使用蛋白质印迹分析比较了口腔鳞状细胞癌细胞系和正常口腔角质形成细胞中Smad4蛋白的表达。在仅60%的口腔鳞状细胞癌组织样本中观察到Smad4表达,而在82%的正常口腔黏膜样本中观察到该表达。与正常口腔角质形成细胞相比,在所有口腔鳞状细胞癌细胞系中均明显观察到Smad4表达降低。这些发现表明,如Smad4表达降低或缺失所示,TGF-β信号通路的异常促进了口腔鳞状细胞癌的致癌作用。