title: Downregulation of p53 promotes in vitro perineural invasive activity of human salivary adenoid cystic carcinoma cells through epithelial-mesenchymal transition-like changes.
abstract: Salivary adenoid cystic carcinoma (SACC) is a malignant tumor that is characterized by perineural invasion (PNI). p53 is an essential tumor-suppressor gene and p53 mutations play a critical role in tumor occurrence and progression (e.g., pancreatic, prostate and head and neck cancer). However, the regulatory role of the p53 gene in SACC and the PNI process remains unknown. In the present study, we employed RNA interference technique to downregulate p53 gene expression in SACC-83 cells to explore the role of p53 in the PNI process. Our results showed that the downregulation of the p53 gene induced significant 'epithelial-mesenchymal transition (EMT)-like changes' in SACC-83 cells, including decreased expression levels of epithelial markers (E-cadherin, EMA and CK5) and increased expression levels of mesenchymal markers (vimentin, N-cadherin and C-cadherin). The downregulation of p53 also caused a lower apoptotic index of Annexin V-FITC/PI and a lower number of SACC-83 cells in the second G0/G1 phase of the cell cycle. Furthermore, the downregulation of the p53 gene resulted in a significant increase in PNI activity in the SACC-83 cells. Thus, our findings revealed that downregulation of p53 promoted in vitro PNI activity through 'EMT-like changes' in SACC-83 cells. The present study suggests the essential regulatory role of p53 in the PNI activity of SACC cells, and implies that p53 may be a new target gene for the clinical treatment of SACC.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Da
authors.initials: D
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ju
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Moyi
authors.initials: M
authors.lastname: Sun
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016192:Resting Phase, Cell Cycle; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D000943:Antigens, Differentiation; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53