| RRC ID |
37727
|
| 著者 |
Tu SP, Chi AL, Ai W, Takaishi S, Dubeykovskaya Z, Quante M, Fox JG, Wang TC.
|
| タイトル |
p53 inhibition of AP1-dependent TFF2 expression induces apoptosis and inhibits cell migration in gastric cancer cells.
|
| ジャーナル |
Am J Physiol Gastrointest Liver Physiol
|
| Abstract |
Overexpression of trefoil factor 2 (TFF2) is associated with increased cell migration, resistance to apoptosis, and possibly increased gastric cancer invasion. Dysregulation of p53 is frequently observed in preneoplastic conditions of the stomach. Here, we investigated the effect of p53 on the expression and function of TFF2 in gastric cancer cell lines. Gene expression was determined by reverse transcription-polymerase chain reaction, and promoter activity was assessed by dual luciferase reporter assays. Apoptosis was detected by flow cytometry, and cell migration was evaluated by the Boyden chamber assay. Exogenous expression of p53 dose dependently inhibited endogenous TFF2 mRNA, protein, and promoter activity and resulted in induction of cell apoptosis and inhibition of cell migration. Downregulation of TFF2 by small interfering RNA sensitized gastric cancer cells to drug-induced p53-dependent apoptosis. Addition of human TFF2 peptide reversed p53-dependent apoptosis and inhibition of cell migration. The p53-responsive element was mapped to an AP-1-like cis-element at -182 bp upstream of the TFF2 transcription start site. Mutation of this AP-1-like element abrogated p53-mediated inhibition of TFF2 promoter activity. Gel shift and chromatin immunoprecipitation assays demonstrated that c-Jun and c-Fos bind to this AP-1-like element. Ectopic expression of c-Jun/c-Fos or p300 or treatment of cells with phorbol 12-myristate 13-acetate (PMA) stimulated endogenous TFF2 mRNA expression and promoter activity, and p53 inhibited the effects of AP-1 and PMA on TFF2. p53 induces cell apoptosis and inhibits cell migration in part by downregulating TFF2 expression through an AP-1-like site, suggesting that TFF2 may be an important downstream target of p53.
|
| 巻・号 |
297(2)
|
| ページ |
G385-96
|
| 公開日 |
2009-8-1
|
| DOI |
10.1152/ajpgi.90620.2008
|
| PII |
90620.2008
|
| PMID |
19541923
|
| PMC |
PMC2724087
|
| MeSH |
Animals
Apoptosis*
Binding Sites
Cell Line, Tumor
Cell Movement*
Down-Regulation
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Mucins / genetics
Mucins / metabolism*
Muscle Proteins / genetics
Muscle Proteins / metabolism*
Mutation
Peptides / genetics
Peptides / metabolism*
Promoter Regions, Genetic
Proto-Oncogene Proteins c-fos / metabolism
Proto-Oncogene Proteins c-jun / metabolism
RNA Interference
Stomach Neoplasms / genetics
Stomach Neoplasms / metabolism*
Stomach Neoplasms / pathology
Transcription Factor AP-1 / genetics
Transcription Factor AP-1 / metabolism*
Transcription, Genetic
Transfection
Trefoil Factor-2
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*
p300-CBP Transcription Factors / metabolism
|
| IF |
3.725
|
| 引用数 |
21
|
|
WOS 分野
|
GASTROENTEROLOGY & HEPATOLOGY
PHYSIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MKN45(RCB1001)
MKN74(RCB1002)
Kato III(RCB2088) |
