IFI16 inhibits tumorigenicity and cell proliferation of bone and cartilage tumor cells

Zhang, Yan; Howell, Ronald Damani; Alfonso, Daniel T.; Yü, Jin; Kong, Li; Wittig, James C.; Liu, Chuanju

doi:10.2741/2433

Cited by 23 publications

(24 citation statements)

References 26 publications

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“…Furthermore, increased expression of cyclin D1 in LNCaP enhanced cell growth and tumorigenicity (Chen et al, 1998;Perry et al, 1998). Therefore, inhibition of cyclin D1 may be an interesting molecular target to control tumor proliferation (Zhang et al, 2007). Our study reveals that metformin may represent a valuable potential therapeutic agent to block prostate tumor growth.…”

Section: Discussionmentioning

confidence: 74%

The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level

et al. 2008

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Metformin is a widely used antidiabetic agent, which regulates glucose homeostasis through inhibition of liver glucose production and an increase in muscle glucose uptake. Recent studies suggest that metformin may reduce the risk of cancer, but its mode of action in cancer remains not elucidated. We investigated the effect of metformin on human prostate cancer cell proliferation in vitro and in vivo. Metformin inhibited the proliferation of DU145, PC-3 and LNCaP cancer cells with a 50% decrease of cell viability and had a modest effect on normal prostate epithelial cell line P69. Metformin did not induce apoptosis but blocked cell cycle in G 0 /G 1 . This blockade was accompanied by a strong decrease of cyclin D1 protein level, pRb phosphorylation and an increase in p27 kip protein expression. Metformin activated the AMP kinase pathway, a fuel sensor signaling pathway. However, inhibition of the AMPK pathway using siRNA against the two catalytic subunits of AMPK did not prevent the antiproliferative effect of metformin in prostate cancer cells. Importantly, oral and intraperitoneal treatment with metformin led to a 50 and 35% reduction of tumor growth, respectively, in mice bearing xenografts of LNCaP. Similar, to the in vitro study, metformin led to a strong reduction of cyclin D1 protein level in tumors providing evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent epidemiological studies.

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Section: Discussionmentioning

confidence: 74%

The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level

et al. 2008

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“…BLAT analysis shows that human FCER1A, DARC, AIM2, PYHIN1, MNDA, IFI16, and APCS genes have undergone extensive sequence evolution, in that little homology is found between the mRNA sequences of human and mouse genomes. Interestingly, AIM2, PYHIN1, IFI16, and DARC all have been shown to have antitumor or tumorsuppressor activity (Ding et al 2004;Chen et al 2006;Zijlstra and Quigley 2006;Zhang et al 2007). New mRNA species not found in mouse genome are also present in this region (e.g., thymus-specific AK057554).…”

Section: Protection Of Tspri Dna Fragments From Exonuclease III Digesmentioning

confidence: 99%

Genome-wide mapping and characterization of hypomethylated sites in human tissues and breast cancer cell lines

Shann¹,

Cheng²,

Chiao³

et al. 2008

Genome Res.

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We have developed a method for mapping unmethylated sites in the human genome based on the resistance of TspRI-digested ends to ExoIII nuclease degradation. Digestion with TspRI and methylation-sensitive restriction endonuclease HpaII, followed by ExoIII and single-strand DNA nuclease allowed removal of DNA fragments containing unmethylated HpaII sites. We then used array comparative genomic hybridization (CGH) to map the sequences depleted by these procedures in human genomes derived from five human tissues, a primary breast tumor, and two breast tumor cell lines. Analysis of methylation patterns of the normal tissue genomes indicates that the hypomethylated sites are enriched in the 5Ј end of widely expressed genes, including promoter, first exon, and first intron. In contrast, genomes of the MCF-7 and MDA-MB-231 cell lines show extensive hypomethylation in the intragenic and intergenic regions whereas the primary tumor exhibits a pattern between those of the normal tissue and the cell lines. A striking characteristic of tumor cell lines is the presence of megabase-sized hypomethylated zones. These hypomethylated zones are associated with large genes, fragile sites, evolutionary breakpoints, chromosomal rearrangement breakpoints, tumor suppressor genes, and with regions containing tissue-specific gene clusters or with gene-poor regions containing novel tissue-specific genes. Correlation with microarray analysis shows that genes with a hypomethylated sequence 2 kb up-or downstream of the transcription start site are highly expressed, whereas genes with extensive intragenic and 3Ј untranslated region (UTR) hypomethylation are silenced. The method described herein can be used for large-scale screening of changes in the methylation pattern in the genome of interest.

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“…Increased expression of IFI16 can trigger senescence and permanent cell growth arrest in epithelial cells, and silencing of the IFI16 gene in these cells may contribute to the development of prostate cancer[106]. Overexpression of IFI16 in human osteosarcoma and chondrosarcoma cell lines inhibits cell proliferation and colony formation, and the level of IFI16 is markedly lower in human osteosarcomas than in normal bone [107]. The IFI16 level inversely correlates with the cancer grade in head and neck squamous cell carcinomas, and ectopic IFI16 reduces both growth rate and invitro transforming activity of a cell line (HNO136) with no detectable expression of IFI16 that was established from a head and neck squamous cell carcinoma tumor [108].…”

Section: Summary and Perspectivesmentioning

confidence: 99%

p204, a p200 family protein, as a multifunctional regulator of cell proliferation and differentiation

Luan

Lengyel

Liu

2008

Cytokine & Growth Factor Reviews

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The interferon-inducible p200 family comprises a group of homologous mouse and human proteins. Most of these have an N-terminal DAPIN domain and one or two partially conserved, 200 amino acid long C-terminal domains (designated as 200X domain). These proteins play important roles in the regulation of cell proliferation, tissue differentiation, apoptosis and senescence. p200 family proteins are involved also in autoimmunity and the control of tumor growth. These proteins function by binding to various target proteins (e.g. transcription factors, signaling proteins, oncoproteins and tumor suppressor proteins) and modulating target activity. This review concentrates on p204, a murine member of the family and its roles in regulating cell proliferation, cell and tissue differentiation (e.g. of skeletal muscle myotubes, beating cardiac myocytes, osteoblasts, chondrocytes and macrophages) and signaling by Ras proteins. The expression of p204 in various tissues as promoted by tissue-specific transcription factors, its distribution among subcellular compartments, and the controls of these features are also discussed.

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IFI16 inhibits tumorigenicity and cell proliferation of bone and cartilage tumor cells

Cited by 23 publications

References 26 publications

The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level

The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level

Genome-wide mapping and characterization of hypomethylated sites in human tissues and breast cancer cell lines

p204, a p200 family protein, as a multifunctional regulator of cell proliferation and differentiation

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