Overexpression of Smad proteins, especially Smad7, in oral epithelial dysplasias.

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.

• Authors: Yuk-Kwan Chen, Anderson Hsien-Cheng Huang, Pei-Hsun Cheng, Shang-Hsun Yang, Li-Min Lin
• Journal: Clinical oral investigations (Clin Oral Investig) Vol. 17 Issue 3 Pg. 921-32 (Apr 2013) ISSN: 1436-3771 [Electronic] Germany
• PMID: 22669485 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• SMAD7 protein, human
• Smad Proteins
• Smad7 Protein

Topics

• Analysis of Variance
• Biomarkers, Tumor
• Carcinoma, Squamous Cell (chemistry, metabolism)
• Cell Proliferation
• Cell Transformation, Neoplastic (metabolism)
• Female
• Focal Epithelial Hyperplasia (metabolism)
• Humans
• Leukoplakia, Oral (chemistry, metabolism)
• Male
• Mouth Mucosa (metabolism, pathology)
• Mouth Neoplasms (chemistry, metabolism)
• Phosphorylation
• Signal Transduction
• Smad Proteins (biosynthesis)
• Smad7 Protein (biosynthesis)
• Statistics, Nonparametric