Downregulation of p53 promotes in vitro perineural invasive activity of human salivary adenoid cystic carcinoma cells through epithelial-mesenchymal transition-like changes
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 r...
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| Veröffentlicht in: | Oncology reports 2015-04, Vol.33 (4), p.1650-1656 |
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| creator | YANG, XIANGMING JING, DA LIU, LIJUN SHEN, ZHIYUAN JU, JUN MA, CHAO SUN, MOYI |
| description | 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. |
| doi_str_mv | 10.3892/or.2015.3750 |
| format | Article |
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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.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2015.3750</identifier><identifier>PMID: 25625376</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Antigens, Differentiation - biosynthesis ; Antigens, Differentiation - genetics ; Apoptosis ; Apoptosis - genetics ; Cancer ; Carcinoma ; Carcinoma, Adenoid Cystic - genetics ; Carcinoma, Adenoid Cystic - pathology ; Cell cycle ; Cell Line, Tumor ; Cell Movement ; Development and progression ; Down-Regulation ; Epithelial-Mesenchymal Transition - genetics ; epithelial-mesenchymal transition-like changes ; G1 Phase ; Gene expression ; Gene Expression Regulation, Neoplastic ; Gene therapy ; Genes, p53 ; Genetic Vectors - genetics ; Genotype & phenotype ; Head & neck cancer ; Health aspects ; Humans ; Medical prognosis ; Metastasis ; Morphology ; Neoplasm Invasiveness - genetics ; Neoplasm Proteins - antagonists & inhibitors ; Neoplasm Proteins - biosynthesis ; Neoplasm Proteins - genetics ; Neoplasm Proteins - physiology ; p53 ; perineural invasion ; Prostate ; Resting Phase, Cell Cycle ; RNA Interference ; RNA, Small Interfering - genetics ; SACC-83 cells ; Salivary Gland Neoplasms - genetics ; Salivary Gland Neoplasms - pathology ; Salivary gland tumors ; Tumor proteins ; Tumor Suppressor Protein p53 - antagonists & inhibitors ; Tumor Suppressor Protein p53 - biosynthesis ; Tumor Suppressor Protein p53 - physiology ; Tumors</subject><ispartof>Oncology reports, 2015-04, Vol.33 (4), p.1650-1656</ispartof><rights>Copyright © 2015, Spandidos Publications</rights><rights>COPYRIGHT 2015 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-8e98c8f4edff447c92d8f7baa44bdad2ce8ad860f5a26fc30de8d597f307e2683</citedby><cites>FETCH-LOGICAL-c486t-8e98c8f4edff447c92d8f7baa44bdad2ce8ad860f5a26fc30de8d597f307e2683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25625376$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>YANG, XIANGMING</creatorcontrib><creatorcontrib>JING, DA</creatorcontrib><creatorcontrib>LIU, LIJUN</creatorcontrib><creatorcontrib>SHEN, ZHIYUAN</creatorcontrib><creatorcontrib>JU, JUN</creatorcontrib><creatorcontrib>MA, CHAO</creatorcontrib><creatorcontrib>SUN, MOYI</creatorcontrib><title>Downregulation of p53 promotes in vitro perineural invasive activity of human salivary adenoid cystic carcinoma cells through epithelial-mesenchymal transition-like changes</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>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.</description><subject>Antigens, Differentiation - biosynthesis</subject><subject>Antigens, Differentiation - genetics</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Cancer</subject><subject>Carcinoma</subject><subject>Carcinoma, Adenoid Cystic - genetics</subject><subject>Carcinoma, Adenoid Cystic - pathology</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Development and progression</subject><subject>Down-Regulation</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>epithelial-mesenchymal transition-like changes</subject><subject>G1 Phase</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene therapy</subject><subject>Genes, p53</subject><subject>Genetic Vectors - genetics</subject><subject>Genotype & phenotype</subject><subject>Head & neck cancer</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>Morphology</subject><subject>Neoplasm Invasiveness - genetics</subject><subject>Neoplasm Proteins - antagonists & inhibitors</subject><subject>Neoplasm Proteins - biosynthesis</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - physiology</subject><subject>p53</subject><subject>perineural invasion</subject><subject>Prostate</subject><subject>Resting Phase, Cell Cycle</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - genetics</subject><subject>SACC-83 cells</subject><subject>Salivary Gland Neoplasms - genetics</subject><subject>Salivary Gland Neoplasms - pathology</subject><subject>Salivary gland tumors</subject><subject>Tumor proteins</subject><subject>Tumor Suppressor Protein p53 - antagonists & inhibitors</subject><subject>Tumor Suppressor Protein p53 - biosynthesis</subject><subject>Tumor Suppressor Protein p53 - physiology</subject><subject>Tumors</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkk1v1DAQhiMEoqVw44wsIVUcyOLYceIcq1I-pEpcQOIWzdrjjYtjBztZtP-pPxJHLS1FyAdbM898-i2KlxXdcNmxdyFuGK3EhreCPiqOq7arSlbz6nF-U1aVnIvvR8WzlK4oZS1tuqfFERMNE7xtjovr9-GXj7hbHMw2eBIMmQQnUwxjmDER68nezjGQCaP1uERw2baHZPdIQM02ew9r1LCM4EkCZ_cQDwQ0-mA1UYc0W0UURGV9GIEodC6ReYhh2Q0EJzsP6Cy4csSEXg2HMVeYI_hk14ZKZ38gUQP4HabnxRMDLuGL2_uk-Pbh4uv5p_Lyy8fP52eXpaplM5cSO6mkqVEbU9et6piWpt0C1PVWg2YKJWjZUCOANUZxqlFq0bWG0xZZI_lJ8eYmb17DzwXT3I82rY2Dx7CkvmqErBkTss3o63_Qq7BEn7vrq47nZG1D6T21A4e99SbkCdWatD-raSsrUckmU5v_UPloHK0KHo3N9gcBp38FDAhuHlJwy7q49BB8ewOqGFKKaPop2jH_U1_RflVRH2K_qqhfVZTxV7dDLdsR9R38Rzb3hdMEXlsd0h0TYlZcSesyL4ny3y4X0lw</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>YANG, XIANGMING</creator><creator>JING, DA</creator><creator>LIU, LIJUN</creator><creator>SHEN, ZHIYUAN</creator><creator>JU, JUN</creator><creator>MA, CHAO</creator><creator>SUN, MOYI</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20150401</creationdate><title>Downregulation of p53 promotes in vitro perineural invasive activity of human salivary adenoid cystic carcinoma cells through epithelial-mesenchymal transition-like changes</title><author>YANG, XIANGMING ; JING, DA ; LIU, LIJUN ; SHEN, ZHIYUAN ; JU, JUN ; MA, CHAO ; SUN, MOYI</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-8e98c8f4edff447c92d8f7baa44bdad2ce8ad860f5a26fc30de8d597f307e2683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Antigens, Differentiation - biosynthesis</topic><topic>Antigens, Differentiation - genetics</topic><topic>Apoptosis</topic><topic>Apoptosis - genetics</topic><topic>Cancer</topic><topic>Carcinoma</topic><topic>Carcinoma, Adenoid Cystic - genetics</topic><topic>Carcinoma, Adenoid Cystic - pathology</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Development and progression</topic><topic>Down-Regulation</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>epithelial-mesenchymal transition-like changes</topic><topic>G1 Phase</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene therapy</topic><topic>Genes, p53</topic><topic>Genetic Vectors - genetics</topic><topic>Genotype & phenotype</topic><topic>Head & neck cancer</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Medical prognosis</topic><topic>Metastasis</topic><topic>Morphology</topic><topic>Neoplasm Invasiveness - genetics</topic><topic>Neoplasm Proteins - antagonists & inhibitors</topic><topic>Neoplasm Proteins - biosynthesis</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - physiology</topic><topic>p53</topic><topic>perineural invasion</topic><topic>Prostate</topic><topic>Resting Phase, Cell Cycle</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - genetics</topic><topic>SACC-83 cells</topic><topic>Salivary Gland Neoplasms - genetics</topic><topic>Salivary Gland Neoplasms - pathology</topic><topic>Salivary gland tumors</topic><topic>Tumor proteins</topic><topic>Tumor Suppressor Protein p53 - antagonists & inhibitors</topic><topic>Tumor Suppressor Protein p53 - biosynthesis</topic><topic>Tumor Suppressor Protein p53 - physiology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>YANG, XIANGMING</creatorcontrib><creatorcontrib>JING, DA</creatorcontrib><creatorcontrib>LIU, LIJUN</creatorcontrib><creatorcontrib>SHEN, ZHIYUAN</creatorcontrib><creatorcontrib>JU, JUN</creatorcontrib><creatorcontrib>MA, CHAO</creatorcontrib><creatorcontrib>SUN, MOYI</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Oncology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>YANG, XIANGMING</au><au>JING, DA</au><au>LIU, LIJUN</au><au>SHEN, ZHIYUAN</au><au>JU, JUN</au><au>MA, CHAO</au><au>SUN, MOYI</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Downregulation of p53 promotes in vitro perineural invasive activity of human salivary adenoid cystic carcinoma cells through epithelial-mesenchymal transition-like changes</atitle><jtitle>Oncology reports</jtitle><addtitle>Oncol Rep</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>33</volume><issue>4</issue><spage>1650</spage><epage>1656</epage><pages>1650-1656</pages><issn>1021-335X</issn><eissn>1791-2431</eissn><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.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>25625376</pmid><doi>10.3892/or.2015.3750</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antigens, Differentiation - biosynthesis Antigens, Differentiation - genetics Apoptosis Apoptosis - genetics Cancer Carcinoma Carcinoma, Adenoid Cystic - genetics Carcinoma, Adenoid Cystic - pathology Cell cycle Cell Line, Tumor Cell Movement Development and progression Down-Regulation Epithelial-Mesenchymal Transition - genetics epithelial-mesenchymal transition-like changes G1 Phase Gene expression Gene Expression Regulation, Neoplastic Gene therapy Genes, p53 Genetic Vectors - genetics Genotype & phenotype Head & neck cancer Health aspects Humans Medical prognosis Metastasis Morphology Neoplasm Invasiveness - genetics Neoplasm Proteins - antagonists & inhibitors Neoplasm Proteins - biosynthesis Neoplasm Proteins - genetics Neoplasm Proteins - physiology p53 perineural invasion Prostate Resting Phase, Cell Cycle RNA Interference RNA, Small Interfering - genetics SACC-83 cells Salivary Gland Neoplasms - genetics Salivary Gland Neoplasms - pathology Salivary gland tumors Tumor proteins Tumor Suppressor Protein p53 - antagonists & inhibitors Tumor Suppressor Protein p53 - biosynthesis Tumor Suppressor Protein p53 - physiology Tumors |
| title | Downregulation of p53 promotes in vitro perineural invasive activity of human salivary adenoid cystic carcinoma cells through epithelial-mesenchymal transition-like changes |
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