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.
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: Gokce A Toruner; Celal Ulger; Mualla Alkan; Anthony T Galante; Joseph Rinaggio; Randall Wilk; Bin Tian; Patricia Soteropoulos; Meera R Hameed; Marvin N Schwalb; James J Dermody Journal: Cancer Genet Cytogenet Date: 2004-10-01
Authors: Matthew A Ginos; Grier P Page; Bryan S Michalowicz; Ketan J Patel; Sonja E Volker; Stefan E Pambuccian; Frank G Ondrey; George L Adams; Patrick M Gaffney Journal: Cancer Res Date: 2004-01-01 Impact factor: 12.701
Authors: Dohun Pyeon; Michael A Newton; Paul F Lambert; Johan A den Boon; Srikumar Sengupta; Carmen J Marsit; Craig D Woodworth; Joseph P Connor; Thomas H Haugen; Elaine M Smith; Karl T Kelsey; Lubomir P Turek; Paul Ahlquist Journal: Cancer Res Date: 2007-05-15 Impact factor: 12.701
Authors: Judith A E M Zecha; Judith E Raber-Durlacher; Raj G Nair; Joel B Epstein; Stephen T Sonis; Sharon Elad; Michael R Hamblin; Andrei Barasch; Cesar A Migliorati; Dan M J Milstein; Marie-Thérèse Genot; Liset Lansaat; Ron van der Brink; Josep Arnabat-Dominguez; Lisette van der Molen; Irene Jacobi; Judi van Diessen; Jan de Lange; Ludi E Smeele; Mark M Schubert; René-Jean Bensadoun Journal: Support Care Cancer Date: 2016-03-16 Impact factor: 3.603
Authors: Johanna Dzieran; Jasmin Fabian; Teng Feng; Cédric Coulouarn; Iryna Ilkavets; Anastasia Kyselova; Kai Breuhahn; Steven Dooley; Nadja M Meindl-Beinker Journal: PLoS One Date: 2013-08-22 Impact factor: 3.240