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p21/waf1 and Smooth-Muscle Actin α Expression in Stromal Fibroblasts of Oral Cancers

Background: Concerted alterations between stromal fibroblasts and neoplastic cells underline the carcinogenic process. Activation of alpha-smooth muscle actin (SMA) expression, a cytoskeleton protein normally expressed only in myoepithelial cells, is considered a landmark for the activation of strom...

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Detalles Bibliográficos
Autores principales: Chatzistamou, Ioulia, Dioufa, Nikolina, Trimis, George, Sklavounou, Alexandra, Kittas, Christos, Kiaris, Hippokratis, Papavassiliou, Athanasios G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605708/
https://www.ncbi.nlm.nih.gov/pubmed/20966541
http://dx.doi.org/10.3233/ACP-CLO-2010-0528
Descripción
Sumario:Background: Concerted alterations between stromal fibroblasts and neoplastic cells underline the carcinogenic process. Activation of alpha-smooth muscle actin (SMA) expression, a cytoskeleton protein normally expressed only in myoepithelial cells, is considered a landmark for the activation of stromal fibroblasts with little however being known regarding the mechanism governing the expression of SMA in the stroma. Methods: We have evaluated by immunohistochemistry the expression of SMA in the stroma of oral malignant and pre-malignant lesions, in association with the expression of p53 and p21 tumor suppressors that were shown previously to be deregulated and/or mutated in stromal fibroblasts of various cancers. The effects of p21 knockdown in SMA expression and cell migration and the mRNA levels of endogenous p21 in fibroblasts co-cultured with cancer cells were also assessed. Results: We found that both p21 and SMA expression was elevated in the stroma, but not the epithelium, of malignant as compared to pre-malignant lesions. We also noted that the expression of both was positively correlated, implying that SMA expression may be regulated by p21. Consistently with this notion we found that siRNA-mediated p21 suppression resulted in the reduction of SMA levels and also inhibited cell migration. Conclusion: Our results show that p21 deregulation is associated with the activation of stromal fibroblasts of oral cancers by a mechanism that involves the stimulation of SMA expression.