Expression of NDRG2 is related to tumor progression and survival of gastric cancer patients through Fas-mediated cell death

Choi, Seung‐Chul; Yoon, Suk Ran; Park, Yuk Pheel; Song, Eun Young; Kim, Jae Wha; Kim, Woo Ho; Yang, Young; Lim, Jong‐Seok; Lee, Hee Gu

doi:10.1038/emm.2007.77

Cited by 74 publications

(71 citation statements)

References 25 publications

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“…Human gastric cancer cell lines SNU1, SNU16, SNU216, SNU484, SNU601, SNU638, SNU668, and SNU719 were originally obtained from the Korean Cell Line Bank (14,15), and these cells were routinely cultured at 37jC in a humidified atmosphere of 5% CO 2 in RPMI 1640 with 10% fetal bovine serum (Sigma).…”

Section: Methodsmentioning

confidence: 99%

Human ZNF312b Promotes the Progression of Gastric Cancer by Transcriptional Activation of the K-ras Gene

Song

Kim

et al. 2009

Cancer Research

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Gastric cancer ranks second among the most common causes of cancer deaths worldwide. Recent studies reported target molecules that are candidates for new therapeutic interventions; however, their molecular mechanism has not been clearly defined. In this study, we found that ZNF312b plays a role in tumor progression and metastasis in gastric cancer via transcriptional activation of the K-ras oncogene. ZNF312b seems to be specifically overexpressed in gastric cancer tissues and cell lines. The overexpression of ZNF312b induces cancerlike phenotypes, including accelerated proliferation and increased tumor masses in nude mice, which are completely reversed by its knockdown in gastric cancer cell lines, implying direct involvement in gastric tumor progression. From analyses using deletion mutants of ZNF312b and K-ras promoter-driven luciferase reporters, we found that it translocates into the nucleus via the proline-rich domain of its COOH terminus to activate transcription of the K-ras gene, resulting in an enhancement of the extracellular signalregulated kinase signaling pathway that governs cell proliferation. Taken together, these results suggest that ZNF312b contributes to the promotion of gastric cancer by triggering K-ras oncogene expression. The current study is the first to report that ZNF312b, a novel transcription factor, was associated with tumorigenicity of gastric cancer. This might be a valuable target that could provide new insight into the development of new therapeutic modalities for patients with gastric cancer. [Cancer Res 2009;69(7):3131-9]

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Section: Methodsmentioning

confidence: 99%

Human ZNF312b Promotes the Progression of Gastric Cancer by Transcriptional Activation of the K-ras Gene

Song

Kim

et al. 2009

Cancer Research

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“…Decreased NDRG2 expression was also found in thyroid carcinomas (Zhao et al, 2008), esophageal squamous cell carcinoma (Shi et al, 2010), and primary AML cells (Tschan et al, 2010). Conversely, overexpression of NDRG2 has been measured in decreased cancer cell growth (Deng et al, 2003;Choi et al, 2007;Yang et al, 2010). NDRG2 can inhibit MSP58 (a 58-kD nuclear microspherule protein)-induced cell proliferation in glioma cells or colon cancer cells (Xu et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of NDRG2 Can Inhibit Neuroblastoma Cell Proliferation through Negative Regulation by CYR61

Zhang

Li²,

Feng³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Several recent studies have showed that the n-myc downstream regulated gene 2 (NDRG2) is a new tumor suppressor gene, and that it plays an important role in tumor suppression in several cancers or cancer cell lines. However, few studies focused on its function in neuroblastoma cells. In the present investigation, we demonstrated that NDRG2 overexpression inhibited their proliferation. Using a cDNA microarray, we found that overexpression of NDRG2 inhibited the expression of cysteine-rich protein 61 (CYR61), a proliferation related gene. From our research, CYR61 may partially hinder NDRG2-mediated inhibition of cell proliferation. Overexpression of NDRG2 resulted in accumulation of cells in the G1 phase, which was accompanied by upregulation of p21 and p27 and downregulation of CDK4 and cyclin D1. Taken together, these data indicate that NDRG2 inhibits the proliferation of neuroblastoma cells partially through suppression of CYR61. Our findings offer novel insights into the physiological roles of NDRG2 in neuroblastoma cell proliferation, and NDRG2 may prove to be effective candidate for the treatment of children with neuroblastoma.

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“…The following antibodies were used: rabbit polyclonal anti-pSTAT3 (Tyr 705), anti-STAT3, anti-PARP (Cell Signaling Technology, Danvers, MA); rabbit anti-p21, rabbit anti-caspase-3, rabbit anti-cytochrome c, goat anti-Bid, rabbit anti-Bcl-x L , goat anti-β-actin (Santa Cruz, CA); and mouse anti-NDRG2 produced by our laboratory (Choi et al, 2007).…”

Section: Chemicals and Antibodiesmentioning

confidence: 99%

“…Recently, it was reported that NDRG2 expression is down-regulated in a variety of carcinomas including liver cancer, pancreatic cancer (Hu et al, 2004), and meningioma (Lusis et al, 2005), and it is also associated with cell growth, differentiation, and apoptosis (Choi et al, 2007). In addition, NDRG2 expression in breast cancer cells has been shown to inhibit STAT3 activation via SOCS1 induction, followed by a decrease in cell proliferation .…”

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confidence: 99%

NDRG2 Expression Increases Apoptosis Induced by Doxorubicin in Malignant Breast Caner Cells

Kim¹,

Kang²,

Yang³

et al. 2009

Biomolecules and Therapeutics

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-N-myc downstream-regulated gene 2 (NDRG2) has recently been found to be a tumor suppressor gene. Although it has been reported that NDRG2 expression in breast cancer cells decreases cell proliferation by inhibiting STAT3 activation via SOCS1 induction, the molecular mechanism of chemotherapeutic agent-induced apoptosis is not well known. To elucidate the effect of NDRG2 on the apoptotic pathway induced by doxorubicin, we established stable cell lines expressing NDRG2 and investigated the effect of NDRG2 expression on the doxorubicin-induced apoptosis. While STAT3 activation was remarkably inhibited by NDRG2 overexpression, the expression level of p21 was increased by NDRG2 expression. We confirmed that NDRG2-expressing cells treated with doxorubicin suppressed STAT3 activation and upregulated p21 expression. NDRG2 expression considerably enhanced TUNEL positive apoptotic cells, poly-ADP ribose polymerase (PARP) cleavage, release of cytochrome c to cytosol, and caspase-3 activity in doxorubicin-induced apoptosis. Bid expression in a resting state and after treatment with doxorubicin increased in MDA-MB-231-NDRG2 cells compared to MDA-MB-231-mock cells. Meanwhile, Bcl-xL expression decreased in MDA-MB-231-NDRG2 cells compared to MDA-MB-231-mock cells in a resting state and in doxorubicin-treated cells. Collectively, these data suggest that suppression of STAT3 activation by NDRG2 influences the sensitivity to doxorubicin-induced apoptosis of breast cancer cells and this may provide a potential therapeutic benefit to overcome the resistance against doxorubicin in breast cancer.

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Expression of NDRG2 is related to tumor progression and survival of gastric cancer patients through Fas-mediated cell death

Cited by 74 publications

References 25 publications

Human ZNF312b Promotes the Progression of Gastric Cancer by Transcriptional Activation of the K-ras Gene

Human ZNF312b Promotes the Progression of Gastric Cancer by Transcriptional Activation of the K-ras Gene

Overexpression of NDRG2 Can Inhibit Neuroblastoma Cell Proliferation through Negative Regulation by CYR61

NDRG2 Expression Increases Apoptosis Induced by Doxorubicin in Malignant Breast Caner Cells

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