Document Detail


Direct evidence for the critical role of NFAT3 in benzo[a]pyrene diol-epoxide-induced cell transformation through mediation of inflammatory cytokine TNF induction in mouse epidermal Cl41 cells.
MedLine Citation:
PMID:  17522069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nuclear factor of activated T cell (NFAT)-3 is a member of the transcription factor NFAT family, which has been demonstrated to be responsible for the up-regulation of the pro-inflammatory cytokine tumor necrosis factor (TNF) in the immune system. Our most recent studies have also shown that TNF is able to induce cell transformation in mouse epidermal Cl41 cells by induction of cyclooxygenase-2 (COX-2) expression. To provide direct evidence for NFAT3 in the environmental carcinogen-caused carcinogenic effect, (+/-)-benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), an ultimate environmental carcinogen metabolized from benzo[a]pyrene, was utilized. We found that exposure of Cl41 cells to B[a]PDE was able to induce cell transformation in Cl41 cells, while specific knock-down of NFAT3 resulted in the dramatic inhibition of this cell transformation. The tumorigenicity of B[a]PDE-caused transformed cells was confirmed in nude mice, whereas the tumor formation of B[a]PDE-treated NFAT3 small interference RNA (siRNA) knock-down cells was significantly reduced. Further studies showed that the role of NFAT3 in B[a]PDE-caused cell transformation was mediated by up-regulation of its downstream targeted gene TNF. This conclusion was based on the findings that inhibition of NFAT3 activation by either FK506 or NFAT3 siRNA dramatically down-regulated the TNF induction upon B[a]PDE exposure, and that knock-down of TNF by its specific siRNA also led to abrogation of B[a]PDE-induced cell transformation in Cl41 cells and their tumorigenicity in nude mice. Collectively, these results provide direct evidence for the important role of NFAT3 activation in B[a]PDE-induced cell transformation by up-regulation of TNF expression in mouse epidermal Cl41 cells, further suggesting that B[a]PDE may exert its tumor promotion effect on skin carcinogenesis, at least partially, by inducing TNF expression.
Authors:
Weiming Ouyang; Yu Hu; Jingxia Li; Min Ding; Yongju Lu; Dongyun Zhang; Yan Yan; Lun Song; Qingshan Qu; Dhimant Desai; Shantu Amin; Chuanshu Huang
Related Documents :
1932719 - Viscoelastic properties of transformed cells: role in tumor cell progression and metast...
902709 - Scanning electron microscopic studies on untreated and transformed mouse embryo fibrobl...
2822959 - Transformation of precrisis human cells by the simian virus 40 cytoplasmic-localization...
2175689 - Functional t-cell subset defined by cluster formation with eb virus transformed b-cells.
1268819 - Cytometric analysis of neoplastic transformation of vertebrate cell populations.
15774489 - Transformation of immortalized colorectal crypt cells by microcystin involving constitu...
10564799 - Transformations of codeine to important semisynthetic opiate derivatives by pseudomonas...
21352549 - Identification of a sub-population of b cells that proliferates after infection with ep...
24017339 - Three-dimensional observation of cell-cell and cell-matrix interactions during myofibri...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-05-23
Journal Detail:
Title:  Carcinogenesis     Volume:  28     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-08     Completed Date:  2007-12-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  2218-26     Citation Subset:  IM    
Affiliation:
Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / toxicity*
Animals
Cell Division
Cell Line
Cell Transformation, Neoplastic*
Epidermis / drug effects,  physiology*
Female
Genes, Reporter
Genetic Vectors
Mice
Mice, Nude
NFATC Transcription Factors / genetics,  physiology*
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha / genetics*
Grant Support
ID/Acronym/Agency:
ES-000260/ES/NIEHS NIH HHS; R01 CA094964/CA/NCI NIH HHS; R01 CA112557/CA/NCI NIH HHS; R01 ES012451/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/NFATC Transcription Factors; 0/RNA, Small Interfering; 0/Tumor Necrosis Factor-alpha; 55097-80-8/7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Promoter hypermethylation is associated with current smoking, age, gender and survival in bladder ca...
Next Document:  Acute hepatotoxicity: a predictive model based on focused illumina microarrays.