| RRC ID |
18616
|
| 著者 |
Higashimura Y, Nakajima Y, Yamaji R, Harada N, Shibasaki F, Nakano Y, Inui H.
|
| タイトル |
Up-regulation of glyceraldehyde-3-phosphate dehydrogenase gene expression by HIF-1 activity depending on Sp1 in hypoxic breast cancer cells.
|
| ジャーナル |
Arch Biochem Biophys
|
| Abstract |
Hypoxia up-regulates the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in a cell type-specific manner. It is unknown whether this occurs in breast cancer. Here, we report that hypoxia up-regulates the GAPDH gene expression through breast cancer-specific molecular mechanisms in MCF-7 cells. Mutation analysis identified a novel hypoxia response element (HRE), in addition to the HRE found previously in prostate cancer LNCaP cells. Knockdown and overexpression of hypoxia-inducible factor (HIF)-1α indicated that HIF-1 contributed to the up-regulation of GAPDH gene expression by hypoxia. Although chromatin immunoprecipitation (ChIP) and plasmid immunoprecipitation analyses revealed the presence of HIF-1α on the novel HRE in both hypoxic cell lines, a mutation in either the novel HRE or its 3'-flanking GC-box resulted in a reduction of hypoxia-increased GAPDH promoter activity only in MCF-7 cells. ChIP analysis showed that Sp1 bound to the GC-box in MCF-7 cells, but not in LNCaP cells, in normoxia and hypoxia. Knockdown of Sp1 reduced hypoxia-increased promoter activity and expression level of GAPDH in MCF-7 cells. These results indicate that in MCF-7 cells, the activation of HIF-1 on the novel HRE contributes to the breast cancer-specific hypoxic induction of GAPDH gene expression and absolutely depends on the presence of Sp1 on the GC-box.
|
| 巻・号 |
509(1)
|
| ページ |
1-8
|
| 公開日 |
2011-5-1
|
| DOI |
10.1016/j.abb.2011.02.011
|
| PII |
S0003-9861(11)00075-0
|
| PMID |
21338575
|
| MeSH |
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Cell Hypoxia*
Cell Line, Tumor
Female
Gene Expression Regulation, Neoplastic*
Glyceraldehyde-3-Phosphate Dehydrogenases / genetics*
Humans
Hypoxia-Inducible Factor 1 / metabolism*
Male
Prostatic Neoplasms / genetics
Prostatic Neoplasms / metabolism
Response Elements
Sp1 Transcription Factor / metabolism*
Transcriptional Activation
Up-Regulation
|
| IF |
3.391
|
| 引用数 |
53
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MCF7(RCB1904)
DU145(RCB2143)
SK-BR-3(RCB2132) |
