Erschienen in:
01.04.2013 | Original Article
Overexpression of Smad proteins, especially Smad7, in oral epithelial dysplasias
verfasst von:
Yuk-Kwan Chen, Anderson Hsien-Cheng Huang, Pei-Hsun Cheng, Shang-Hsun Yang, Li-Min Lin
Erschienen in:
Clinical Oral Investigations
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Ausgabe 3/2013
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Abstract
Objective
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).
Materials and methods
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.
Results
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.
Conclusions
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.
Clinical relevance
Smad7 could be a marker for risk of malignant transformation of oral epithelial dysplasia.