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.
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 p21tumor 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.
Authors: W S el-Deiry; T Tokino; V E Velculescu; D B Levy; R Parsons; J M Trent; D Lin; W E Mercer; K W Kinzler; B Vogelstein Journal: Cell Date: 1993-11-19 Impact factor: 41.582
Authors: J Bar; R Feniger-Barish; N Lukashchuk; H Shaham; N Moskovits; N Goldfinger; D Simansky; M Perlman; M Papa; A Yosepovich; G Rechavi; V Rotter; M Oren Journal: Oncogene Date: 2008-12-08 Impact factor: 9.867
Authors: Paul Yaswen; Karen L MacKenzie; W Nicol Keith; Patricia Hentosh; Francis Rodier; Jiyue Zhu; Gary L Firestone; Ander Matheu; Amancio Carnero; Alan Bilsland; Tabetha Sundin; Kanya Honoki; Hiromasa Fujii; Alexandros G Georgakilas; Amedeo Amedei; Amr Amin; Bill Helferich; Chandra S Boosani; Gunjan Guha; Maria Rosa Ciriolo; Sophie Chen; Sulma I Mohammed; Asfar S Azmi; Dipita Bhakta; Dorota Halicka; Elena Niccolai; Katia Aquilano; S Salman Ashraf; Somaira Nowsheen; Xujuan Yang Journal: Semin Cancer Biol Date: 2015-04-11 Impact factor: 15.707