論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MCF7(RCB1904) DU145(RCB2143) SK-BR-3(RCB2132) |