論文 - 詳細
| RRC ID | 18134 |
|---|---|
| 著者 | Lin WH, Martin JL, Marsh DJ, Jack MM, Baxter RC. |
| タイトル | Involvement of insulin-like growth factor-binding protein-3 in the effects of histone deacetylase inhibitor MS-275 in hepatoma cells. |
| ジャーナル | J Biol Chem |
| Abstract |
Insulin-like growth factor-binding protein-3 (IGFBP-3) expression is frequently suppressed in liver cancers and can be reactivated by histone deacetylase (HDAC) inhibition. This study examined the role of IGFBP-3 in mediating the effects of the HDAC inhibitor MS-275 in liver cancer cells and identified IGFBP-3-dependent proteins that regulate proliferation and migration. In HepG2 cells, MS-275 inhibited DNA synthesis, cell cycle activity, and cell viability concomitantly with increased binding of acetylated histone H3 to IGFBP-3 promoter sequences and induction of IGFBP-3 expression. IGFBP-3 down-regulation by siRNA significantly reversed the inhibition of cell viability and DNA synthesis by MS-275, indicating an intermediary role for IGFBP-3. Induction of the cyclin-dependent kinase inhibitor p21 by MS-275 was attenuated by IGFBP-3 down-regulation, providing an explanation for IGFBP-3-dependent effects of MS-275 on cell cycle activity. In contrast, MS-275 stimulated HepG2 cell migration, an effect also inhibited by IGFBP-3 down-regulation. Among genes whose induction by MS-275 was attenuated by IGFBP-3 down-regulation, LYVE1 and THBS2 (thrombospondin-2) were identified as mediators of IGFBP-3-dependent effects of MS-275. Silencing of either protein had no effect on the inhibition of HepG2 viability by MS-275 but reversed its stimulatory effect on cell migration. We conclude that among genes up-regulated by MS-275, IGFBP-3 is a key mediator of effects on hepatoma cell growth and migration, involving IGFBP-3-dependent proteins p21 (proliferation) and LYVE1 and THBS2 (migration). The enhanced cell motility that accompanies reactivation of IGFBP-3 expression in liver cancer by HDAC inhibition suggests the possibility of increased metastatic spread despite inhibited cell proliferation. |
| 巻・号 | 286(34) |
| ページ | 29540-7 |
| 公開日 | 2011-8-26 |
| DOI | 10.1074/jbc.M111.263111 |
| PII | S0021-9258(19)76030-X |
| PMID | 21737444 |
| PMC | PMC3190994 |
| MeSH | Acetylation / drug effects Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism Benzamides / pharmacology* Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism* Cell Cycle / drug effects Cell Cycle / genetics Cell Movement / drug effects Cell Movement / genetics Cell Survival / drug effects Cell Survival / genetics Down-Regulation / drug effects Down-Regulation / genetics Gene Expression Regulation, Neoplastic / drug effects* Gene Expression Regulation, Neoplastic / genetics Gene Silencing / drug effects Hep G2 Cells Histone Deacetylase Inhibitors / pharmacology* Histones / genetics Histones / metabolism Humans Insulin-Like Growth Factor Binding Protein 3 Insulin-Like Growth Factor Binding Proteins / biosynthesis* Insulin-Like Growth Factor Binding Proteins / genetics Liver Neoplasms / genetics Liver Neoplasms / metabolism* Neoplasm Proteins / biosynthesis* Neoplasm Proteins / genetics Pyridines / pharmacology* Repressor Proteins / genetics Repressor Proteins / metabolism Thrombospondins / genetics Thrombospondins / metabolism Vesicular Transport Proteins / genetics Vesicular Transport Proteins / metabolism |
| IF | 4.238 |
| 引用数 | 11 |
| WOS 分野 | 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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| 各媒体での言及数の合計 | 0 |
| 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 | HuH-6(RCB1367) |