Nucleotide variations in genes encoding plasminogen activator inhibitor-2 and serine proteinase inhibitor B10 associated with prostate cancer

Shioji, Go; Ezura, Yoichi; Nakajima, Toshiaki; Ohgaki, Kenji; Fujiwara, Hiromichi; Kubota, Yoshinobu; Ichikawa, Tomohiko; Inoue, Katsuki; Shuin, Taro; Habuchi, Tomonori; Ogawa, Osamu; Nishimura, Takuya; Emi, Mitsuru

doi:10.1007/s10038-005-0285-1

Cited by 12 publications

(10 citation statements)

References 21 publications

(20 reference statements)

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“…Genes encoding class B ( SERPINB s) are clustered in two chromosomal regions, 18q21 and 6q25. However, all of the SERPINB genes that appear to be involved in cancer etiology localize together to 18q21 [24]. Based on gene expression microarray data of EP156T cells and PC3 cells, we found that all SERPINB s in 18q21 were silenced in PC3 cells, while 7 out of 10 were highly expressed in EP156T cells.…”

Section: Resultsmentioning

confidence: 82%

Genome-Wide Profiling of Histone H3 Lysine 4 and Lysine 27 Trimethylation Reveals an Epigenetic Signature in Prostate Carcinogenesis

et al. 2009

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BackgroundIncreasing evidence implicates the critical roles of epigenetic regulation in cancer. Very recent reports indicate that global gene silencing in cancer is associated with specific epigenetic modifications. However, the relationship between epigenetic switches and more dynamic patterns of gene activation and repression has remained largely unknown.Methodology/Principal FindingsGenome-wide profiling of the trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) was performed using chromatin immunoprecipitation coupled with whole genome promoter microarray (ChIP-chip) techniques. Comparison of the ChIP-chip data and microarray gene expression data revealed that loss and/or gain of H3K4me3 and/or H3K27me3 were strongly associated with differential gene expression, including microRNA expression, between prostate cancer and primary cells. The most common switches were gain or loss of H3K27me3 coupled with low effect on gene expression. The least prevalent switches were between H3K4me3 and H3K27me3 coupled with much higher fractions of activated and silenced genes. Promoter patterns of H3K4me3 and H3K27me3 corresponded strongly with coordinated expression changes of regulatory gene modules, such as HOX and microRNA genes, and structural gene modules, such as desmosome and gap junction genes. A number of epigenetically switched oncogenes and tumor suppressor genes were found overexpressed and underexpressed accordingly in prostate cancer cells.Conclusions/SignificanceThis work offers a dynamic picture of epigenetic switches in carcinogenesis and contributes to an overall understanding of coordinated regulation of gene expression in cancer. Our data indicate an H3K4me3/H3K27me3 epigenetic signature of prostate carcinogenesis.

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Section: Resultsmentioning

confidence: 82%

Genome-Wide Profiling of Histone H3 Lysine 4 and Lysine 27 Trimethylation Reveals an Epigenetic Signature in Prostate Carcinogenesis

et al. 2009

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“…35 A report has shown in the SERPINB10 gene two other missense variations (rs8097425 and rs963075) conferring important risks for prostate cancer. 36 The LGP2 gene is 21 kb away from HSPB9 in the reverse direction. LGP2, a RNA helicase with multiple functionally important domains, is involved in the regulation of interferon production, and thus has potential therapeutic implications for immune regulation.…”

Section: Discussionmentioning

confidence: 99%

Genetic Architecture of Transcript-Level Variation in Humans

Duan

Huang

Zhang

et al. 2008

The American Journal of Human Genetics

125

127

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We report here the results of testing the pairwise association of 12,747 transcriptional gene-expression values with more than two million single-nucleotide polymorphisms (SNPs) in samples of European (CEPH from Utah; CEU) and African (Yoruba from Ibadan; YRI) ancestry. We found 4,677 and 5,125 significant associations between expression quantitative nucleotides (eQTNs) and transcript clusters in the CEU and the YRI samples, respectively. The physical distance between an eQTN and its associated transcript cluster was referred to as the intrapair distance. An association with 4 Mb or less intrapair distance was defined as local; otherwise, it was defined as distant. The enrichment analysis of functional categories shows that genes harboring the local eQTNs are enriched in the categories related to nucleosome and chromatin assembly; the genes harboring the distant eQTNs are enriched in the categories related to transmembrane signal transduction, suggesting that these biological pathways are likely to play a significant role in regulation of gene expression. We highlight in the EPHX1 gene a deleterious nonsynonymous SNP that is distantly associated with gene expression of ORMDL3, a susceptibility gene for asthma.

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“…At least two sequence variants of SerpinB2 are known which differ by three amino acids and these polymorphisms have been associated with increased risk of stroke and prostate cancer (64,65). Two other non-synonymous single nucleotide polymorphisms (SNPs) have been identified in the coding sequence of SerpinB2 (rs17850949, rs6100), indicating that additional variants exist.…”

Section: Discussionmentioning

confidence: 99%

SerpinB2 Is an Inducible Host Factor Involved in Enhancing HIV-1 Transcription and Replication

Darnell¹,

Schroder²,

Gardner³

et al. 2006

J. Biol. Chem.

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The serine protease inhibitor SerpinB2 (plasminogen activator inhibitor-2) is a major product of activated monocytes and macrophages and is substantially induced during most inflammatory processes. Distinct from its widely described extracellular role as an inhibitor of urokinase plasminogen activator, SerpinB2 has recently been shown to have an intracellular role as a retinoblastoma protein (Rb)-binding protein that inhibits Rb degradation. Here we show that HIV-1 infection and gp120 treatment of human peripheral blood mononuclear cells resulted in induction of SerpinB2. Furthermore, SerpinB2 expression in THP-1 monocyte/macrophage, Jurkat T, and HeLa cell lines increased replication of HIV-1 and enhanced transcription from the HIV-1 long terminal repeat (LTR) promoter by 3-10-fold. Increased HIV-1 gene expression and transcription was also observed in activated macrophages from SerpinB2 ؉/؉ mice compared with macrophages from SerpinB2 ؊/؊ mice. The SerpinB2-mediated elevation of Rb protein levels appeared to be responsible for enhancing transcription from the core promoter region of the LTR by relieving HDM2-mediated inhibition of Sp1 and/or by increasing the Sp1/Sp3 expression ratios. This is the first report associating HIV-1 replication with SerpinB2 expression and illustrates that SerpinB2 is a potentially important inducible host factor that significantly promotes HIV-1 replication.SerpinB2, also known as plasminogen activator inhibitor type-2 (PAI-2), 2 is one of the most abundant proteins of activated monocytes and macrophages, whose expression is substantially up-regulated during most inflammatory processes (1, 2). SerpinB2 is also induced following infection with a range of parasitic (3, 4), viral (5-8), and bacterial (9 -12) pathogens. Although SerpinB2 is widely described as an inhibitor of the extracellular urokinase plasminogen activator, the evidence that SerpinB2 has a major physiological role in the regulation of plasminogen activation is not compelling (13). SerpinB2 is a member of the Clade B or ovalbumin-like serine protease inhibitor (ov-serpin) subgroup of serpins, which lack a classical secretory signal peptide and are frequently found to reside intracellularly with a cytoplasmic or nucleocytoplasmic distribution (14). SerpinB2 has recently been shown to have an intranuclear activity as a retinoblastoma protein (Rb)-binding protein (15-18). SerpinB2 expression inhibited Rb degradation, which resulted in increased Rb protein levels. This activity required both (i) the C-D interhelical region of SerpinB2, which mediates Rb binding, and (ii) the reactive site loop (RSL), which mediates the protease inhibitory activity of SerpinB2. The SerpinB2-mediated increase in Rb protein levels was found to enhance Rb-mediated activities, such as repression of E2F-1-dependent gene expression and promotion of G 1 cell cycle arrest (15). SerpinB2 expression has also been shown to influence transcription of mammalian (15, 19) and viral genes (16), with the latter two studies illustrating that this activity ...

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Nucleotide variations in genes encoding plasminogen activator inhibitor-2 and serine proteinase inhibitor B10 associated with prostate cancer

Cited by 12 publications

References 21 publications

Genome-Wide Profiling of Histone H3 Lysine 4 and Lysine 27 Trimethylation Reveals an Epigenetic Signature in Prostate Carcinogenesis

Genome-Wide Profiling of Histone H3 Lysine 4 and Lysine 27 Trimethylation Reveals an Epigenetic Signature in Prostate Carcinogenesis

Genetic Architecture of Transcript-Level Variation in Humans

SerpinB2 Is an Inducible Host Factor Involved in Enhancing HIV-1 Transcription and Replication

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