Silencing the Metallothionein-2A gene inhibits cell cycle progression from G1- to S-phase involving ATM and cdc25A signaling in breast cancer cells

Lim, Daina; Jocelyn, Koh Mei-Xin; Yip, George; Bay, Boon‐Huat

doi:10.1016/j.canlet.2008.10.038

Cited by 46 publications

(38 citation statements)

References 44 publications

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“…This suggests that eIF3m influences the expression of a designated subset of genes for cell proliferation and tumor progression by affecting the mRNA level. In addition, as Lim et al (2009) reported that MT2A silencing resulted in cell division cycle 25 homolog A (CDC25A) degradation and G1-arrest in breast cancer cells, we found that eIF3m silencing immediately decreased CDC25A from 24 h until 72 h (Figure 8). These results further support that eIF3m expression influences the cell cycle regulation.…”

Section: Identification Of Eif3m-associated Transcripts By Ribonomicsmentioning

confidence: 69%

“…This suggests that eIF3m expression has an effect in regulating mRNA levels of a specific subset of genes associated with cell proliferation and tumor progression. Further support for this hypothesis is provided by the reduced expression of MT2A resulting from ubiquitindependent degradation of CDC25A, which is necessary for the progression from G1 to S phase of the cell cycle via ATM/Chk2 in a breast cancer model (Lim et al, 2009). Although HCT-116 colon cancer cells showed subG0/G1 arrest rather than G1 arrest and S phase reduction with CDC25A loss as it was reported (Tomko et al, 2009), we supposed that this difference came from the different cell property of HCT-116 from breast cancer cells, MCF-7 or MCF12.…”

Section: Discussionmentioning

confidence: 97%

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eIF3m expression influences the regulation of tumorigenesis-related genes in human colon cancer

Hong

et al. 2010

Oncogene

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Abnormal regulation of gene expression is essential for tumorigenesis. Recent studies indicate that regulation of oncogene expression and neoplastic transformation are controlled by subunits of eukaryotic translation initiation factors (eIFs). Here we focused on eIF3 performing a pivotal role in protein synthesis and the differential expression of its subunits in cancer. The most uncharacterized non-core subunit eIF3m was confirmed to be highly expressed in human cancer cell lines and colon cancer patient tissues. By expression silencing with eIF3m-specific small interfering RNA (siRNA), we confirmed that eIF3m influences cell proliferation, cell cycle progression and cell death in human colon cancer cell line HCT-116. Using a ribonomics approach, we identified a subset of elF3m-influenced genes and showed that the expression of two highly represented tumorigenesis-related genes, MIF and MT2, were affected by eIF3m at the mRNA level. We also confirmed eIF3m-dependent regulation of MT2A downstream molecule CDC25A, which is necessary for cell cycle progression in HCT-116 cells. These results suggest that eIF3m mediates regulation of tumorigenesis-related genes in human colon cancer. Further investigations on tumorigenesis-related genes and their regulation by eIFs will provide clues for designing targeted therapy for cancer.

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Section: Identification Of Eif3m-associated Transcripts By Ribonomicsmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 97%

eIF3m expression influences the regulation of tumorigenesis-related genes in human colon cancer

Hong

et al. 2010

Oncogene

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“…In cultured human Chang (CCl-13) hepatocytes, cell proliferation is associated with a 3-5 fold increase of metallothionein [44]. Conversely, down-regulation of the metallothionein-2A gene causes cell cycle arrest in the G1 phase [45]. These findings suggest a function of metallothionein in controlling cellular Zn 2+ availability for the activation/inhibition of zinc proteins involved in cell proliferation.…”

Section: Discussionmentioning

confidence: 94%

Transient fluctuations of intracellular zinc ions in cell proliferation

Maret

2009

Experimental Cell Research

100

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“…18) More recently, silencing of the MT2A gene inhibited cell cycle progression in breast cancer cells. 19) MT2A mRNA expression was reduced in NHBE and DHBE (COPD) cells by SWCNT exposure. Therefore, the decrease in MT2A gene expression in the present study might have some consequence on the regulation of cell cycle progression.…”

Section: Discussionmentioning

confidence: 96%

Single-Walled Carbon Nanotubes Downregulate Stress-Responsive Genes in Human Respiratory Tract Cells

Hitoshi

Katoh

Suzuki

et al. 2012

Biological & Pharmaceutical Bulletin

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Carbon nanotubes (CNTs) are currently key promising materials of nanotechnology. However, elucidation of the possible effects of CNTs on the respiratory tract is urgently needed. The present study aimed to clarify the effect of single-walled CNTs (SWCNTs) on the expression of stress-responsive genes, using primary cultured normal human bronchial epithelial (NHBE), diseased HBE (DHBE) cells, and the human carcinoma cell lines A549 and FaDu. Purified SWCNTs were applied at concentrations of 0.1 or 1.0 mg/mL for 6 h, and a polymerase chain reaction (PCR) array was conducted to examine 84 stress-responsive genes. NHBE cell exposure to SWCNTs resulted in global downregulation of genes involved in inflammation, oxidative stress, and apoptosis. Further analysis using DHBE cells and carcinoma cell lines indicated a similar trend, although differences in sensitivity were observed. Downregulation of stress-responsive genes may be involved in the mechanism by which stress response protects against lung injury.Key words carbon nanotube; stress-responsive gene; human bronchial epithelial cell Nanotechnology has drastically emerged over the past 10 years, and a vast variety of nanomaterials, which can be employed in a wide range of applications in nanoscience, medicine, and engineering, have been created. Carbon nanotubes (CNTs), discovered by Iijima, are currently key promising materials of nanotechnology.

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Silencing the Metallothionein-2A gene inhibits cell cycle progression from G1- to S-phase involving ATM and cdc25A signaling in breast cancer cells

Cited by 46 publications

References 44 publications

eIF3m expression influences the regulation of tumorigenesis-related genes in human colon cancer

eIF3m expression influences the regulation of tumorigenesis-related genes in human colon cancer

Transient fluctuations of intracellular zinc ions in cell proliferation

Single-Walled Carbon Nanotubes Downregulate Stress-Responsive Genes in Human Respiratory Tract Cells

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