Silencing the Metallothionein-2A gene inhibits cell cycle progression from G1- to S-phase involving ATM and cdc25A signaling in breast cancer cells
| Autor: | Daina Lim, George W. Yip, Boon-Huat Bay, Koh Mei-Xin Jocelyn |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Cell cycle checkpoint Cellular differentiation Blotting Western Down-Regulation Gene Expression Breast Neoplasms Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases Biology S Phase Cell Line Tumor Humans cdc25 Phosphatases Gene silencing Gene Silencing RNA Messenger CHEK1 RNA Small Interfering Cell Proliferation Reverse Transcriptase Polymerase Chain Reaction Cell growth Tumor Suppressor Proteins Cell Cycle G1 Phase Cell cycle Flow Cytometry Molecular biology Cell biology DNA-Binding Proteins Checkpoint Kinase 2 Oncology Cell culture Microscopy Electron Scanning Female Metallothionein A431 cells Signal Transduction |
| Zdroj: | Cancer Letters. 276:109-117 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2008.10.038 |
| Popis: | Metallothioneins (MTs) are a group of metal-binding proteins involved in cell proliferation, differentiation and apoptosis. The MT-2A isoform is generally the most abundant isoform among the 10 known functional MT genes. In the present study, we observed that down-regulation of the MT-2A gene in MCF-7 cells via siRNA-mediated silencing inhibited cell growth by inducing cell cycle arrest in G1-phase (G1-arrest) and a marginal increase in cells in sub-G1-phase. Scanning electron microscopic examination of the cells with silenced expression of MT-2A (siMT-2A cells) revealed essentially normal cell morphology with presence of scattered apoptotic cells. To elucidate the underlying molecular mechanism, we examined the expression of cell cycle related genes in MT-2A-silenced cells and found a higher expression of the ataxia telangiectasia mutated (ATM) gene concomitant with a lower expression of the cdc25A gene. These data suggest that MT-2A could plausibly modulate cell cycle progression from G1- to S-phase via the ATM/Chk2/cdc25A pathway. |
| Databáze: | OpenAIRE |
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