| RRC ID |
68812
|
| 著者 |
Endo F, Nishizuka SS, Kume K, Ishida K, Katagiri H, Ishida K, Sato K, Iwaya T, Koeda K, Wakabayashi G.
|
| タイトル |
A compensatory role of NF-κB to p53 in response to 5-FU-based chemotherapy for gastric cancer cell lines.
|
| ジャーナル |
PLoS One
|
| Abstract |
Despite of remarkable improvement of postoperative 5-FU-based adjuvant chemotherapy, the relapse rate of gastric cancer patients who undergo curative resection followed by the adjuvant chemotherapy remains substantial. Therefore, it is important to identify prediction markers for the chemotherapeutic efficacy of 5-FU. We recently identified NF-κB as a candidate relapse prediction biomarker in gastric cancer. To evaluate the biological significance of NF-κB in the context of 5-FU-based chemotherapy, we analyzed the NF-κB-dependent biological response upon 5-FU treatment in gastric cancer cell lines. Seven genes induced by 5-FU treatment in an NF-κB-dependent manner were identified, five of which are known p53 targets. Knockdown of RELA, which encodes the p65 subunit of NF-κB, decreased both p53 and p53 target protein levels. In contrast, NF-κB was not affected by TP53 knockdown. We also demonstrated that cell lines bearing Pro/Pro homozygosity in codon72 of p53 exon4, which is important for NF-κB binding to p53, are more resistant to 5-FU than those with Arg/Arg homozygosity. We conclude that NF-κB plays an important role in the response to 5-FU treatment in gastric cancer cell lines, with a possible compensatory function of p53. These results suggest that NF-κB is a potential 5-FU-chemosensitivity prediction marker that may reflect 5-FU-induced stress-response pathways, including p53.
|
| 巻・号 |
9(2)
|
| ページ |
e90155
|
| 公開日 |
2014-1-1
|
| DOI |
10.1371/journal.pone.0090155
|
| PII |
PONE-D-13-42642
|
| PMID |
24587255
|
| PMC |
PMC3937424
|
| MeSH |
Antimetabolites, Antineoplastic / pharmacology*
Antimetabolites, Antineoplastic / therapeutic use
Cell Line, Tumor
Codon
Drug Resistance, Neoplasm / genetics
Fluorouracil / pharmacology*
Fluorouracil / therapeutic use
Gene Expression Profiling
Gene Expression Regulation, Neoplastic / drug effects
Gene Knockdown Techniques
Humans
NF-kappa B / metabolism*
Protein Binding
Protein Transport
Stomach Neoplasms / drug therapy
Stomach Neoplasms / genetics
Stomach Neoplasms / metabolism*
Transcription Factor RelA / genetics
Transcription Factor RelA / metabolism
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*
|
| IF |
2.74
|
| リソース情報 |
| ヒト・動物細胞 |
Kato III(RCB2088)
MKN74(RCB1002)
NUGC-4(RCB1939)
GSS(RCB2277)
GCIY(RCB0555)
MKN45(RCB1001) |
