Division of Oral Pathology and Diagnosis, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan.
Clin Oral Investig. 2013 Apr;17(3):921-32. doi: 10.1007/s00784-012-0756-7. Epub 2012 Jun 6.
Transforming growth factor β, via membrane-bound receptors and downstream Smad2-4, 7, can modulate tumorigenesis. Smad2 and Smad3 heterodimerize with Smad4, and the complex migrates to the nucleus to regulate the expression of target genes. Smad7 is a key negative regulator of this signaling pathway. This study aimed to examine Smad2-4, 7 expression and phosphorylated Smad2-3 (p-Smad2-3) in oral epithelial dysplasia and compared it with normal oral mucosa, hyperkeratosis/epithelial hyperplasia and squamous cell carcinoma (SCC).
Immunohistochemical staining of Smad2-4, 7 and p-Smad2-3, was performed for 75 samples of human oral mucosa, including hyperkeratosis/epithelial hyperplasia (n = 20), mild epithelial dysplasia (n = 11), moderate to severe epithelial dysplasia (n = 11), and SCC (n = 43). Normal buccal mucosa samples (n = 9) were also included.
A significant increase in Smad7 expression was observed in the ascending order of samples of normal oral mucosa, hyperkeratosis/epithelial hyperplasia/mild oral epithelial dysplasia, moderate to severe oral epithelial dysplasia, and well-differentiated oral SCC/moderately to poorly differentiated oral SCC. Additionally, significant increases in Smad7 expression were noted as compared with expression of Smad2-4 and p-Smad2-3 in lesions of hyperkeratosis/epithelial hyperplasia, mild oral epithelial dysplasia, moderate to severe oral epithelial dysplasia, well-differentiated oral SCC, and moderately to poorly differentiated oral SCC.
Our results indicate that Smad proteins, particularly Smad7, in oral epithelial dysplasia and SCC could contribute to the attenuation of Smads anti-proliferative signaling in cancer development.
Smad7 could be a marker for risk of malignant transformation of oral epithelial dysplasia.
转化生长因子β通过膜结合受体和下游的 Smad2-4、7 可以调节肿瘤发生。Smad2 和 Smad3 与 Smad4 形成异二聚体，复合物迁移到细胞核调节靶基因的表达。Smad7 是该信号通路的关键负调控因子。本研究旨在检测口腔上皮异型增生中 Smad2-4、7 的表达及磷酸化 Smad2-3（p-Smad2-3），并与正常口腔黏膜、角化过度/上皮增生和鳞状细胞癌（SCC）进行比较。
对 75 例人口腔黏膜标本进行 Smad2-4、7 和 p-Smad2-3 的免疫组织化学染色，包括角化过度/上皮增生（n=20）、轻度上皮异型增生（n=11）、中重度上皮异型增生（n=11）和 SCC（n=43）。还包括正常颊黏膜标本（n=9）。
Smad7 的表达随着正常口腔黏膜、角化过度/上皮增生/轻度口腔上皮异型增生、中重度口腔上皮异型增生、高分化口腔 SCC/中低分化口腔 SCC 样本的顺序呈显著递增。与角化过度/上皮增生、轻度口腔上皮异型增生、中重度口腔上皮异型增生、高分化口腔 SCC、中低分化口腔 SCC 病变中的 Smad2-4 和 p-Smad2-3 相比，Smad7 的表达也显著增加。
我们的结果表明，口腔上皮异型增生和 SCC 中的 Smad 蛋白，特别是 Smad7，可能有助于减弱 Smads 抗增殖信号在癌症发展中的作用。
Smad7 可能是口腔上皮异型增生恶变风险的标志物。
