| RRC ID |
44831
|
| 著者 |
Xue M, Fang Y, Sun G, Zhuo W, Zhong J, Qian C, Wang L, Wang L, Si J, Chen S.
|
| タイトル |
IGFBP3, a transcriptional target of homeobox D10, is correlated with the prognosis of gastric cancer.
|
| ジャーナル |
PLoS One
|
| Abstract |
Homeobox D10 (HoxD10) plays important roles in the differentiation of embryonic cells and progression of breast cancer. Our previous report revealed that insulin-like growth factor binding protein-3 (IGFBP3) was regulated by HoxD10 in gastric cancer cells; however, the functional roles and underlying mechanisms of IGFBP3 in gastric cancer remain unclear. Here, we found that the expression of IGFBP3 were upregulated after ectopic expression of HoxD10 in gastric cancer cells. Chromatin immunoprecipitation assay showed that HoxD10 bound to three potential regions of IGFBP3 promoter. Exogenous HoxD10 significantly enhanced the activity of luciferase reporter containing these binding regions in gastric cancer cells. Further data showed that all of these binding sites had Hox binding element "TTAT". Immunohistochemical staining results revealed that IGFBP3 expression was significantly downregulated in 86 gastric adenocarcinomas tissues relative to their adjacent non-cancerous tissues (p<0.001). Moreover, IGFBP3 expression was significantly lower in gastric tumor with lymph node metastasis compared with that without lymph node metastasis (p=0.045). Patients with high expression level of IGFBP3 showed favorable 5 year overall survival (p=0.011). Knockdown of IGFBP3 accelerated gastric cancer cell migration and invasion and induced the expression of invasive factors including MMP14, uPA and uPAR. Thus, our data suggest that HoxD10-targeted gene IGFBP3 may suppress gastric cancer cell invasion and favors the survival of gastric cancer patients.
|
| 巻・号 |
8(12)
|
| ページ |
e81423
|
| 公開日 |
2013-1-1
|
| DOI |
10.1371/journal.pone.0081423
|
| PII |
PONE-D-13-25905
|
| PMID |
24386080
|
| PMC |
PMC3873913
|
| MeSH |
Cell Line, Tumor
Cell Movement / genetics
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Homeodomain Proteins / genetics
Homeodomain Proteins / physiology
Humans
Immunohistochemistry
Insulin-Like Growth Factor Binding Protein 3 / genetics*
Matrix Metalloproteinase 14 / genetics
Matrix Metalloproteinase 14 / metabolism
Neoplasm Invasiveness / genetics
Prognosis
Promoter Regions, Genetic
Receptors, Urokinase Plasminogen Activator / genetics
Receptors, Urokinase Plasminogen Activator / metabolism
Stomach Neoplasms / diagnosis
Stomach Neoplasms / genetics*
Survival Analysis
Transcription Factors / genetics
Transcription Factors / physiology
Up-Regulation
Urokinase-Type Plasminogen Activator / genetics
Urokinase-Type Plasminogen Activator / metabolism
|
| IF |
2.74
|
| 引用数 |
16
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MKN28(RCB1000)
MKN45(RCB1001)
HGC-27(RCB0500) |
