Publications (21)73.99 Total impact
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Article: TLS-CHOP represses miR-486 expression, inducing upregulation of a metastasis regulator PAI-1 in human myxoid liposarcoma.
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ABSTRACT: Myxoid liposarcomas (MLSs) are characterized by t(12;16)(q13;p11) translocation and expression of TLS-CHOP chimeric oncoprotein. However, the molecular functions of TLS-CHOP have not been fully understood. On the other hand, microRNAs (miRNAs) comprise an abundant class of endogenous small non-coding RNAs that negatively regulate the expression of their target genes, and are involved in many biological processes. It is now evident that dysregulation of miRNAs is an important step in the development of many cancers. To our knowledge, however, there have been no reports of the miRNAs involved in MLS tumorigenesis and development. In this study, we have found that miR-486 expression was repressed in TLS-CHOP-expressed NIH3T3 fibroblasts and MLS tissues, and exogenous overexpression of miR-486 repressed growth of MLS cells. Thus, downregulation of miR-486 may be an important process for MLS. In addition, we have identified plasminogen activator inhibitor-1 (PAI-1) as a novel target gene of miR-486. PAI-1 is a unique type of serine protease inhibitor and is known to be one of the key regulators of tumor invasion and metastasis. Furthermore, knockdown of PAI-1 by a specific small interfering RNA (siRNA) inhibited growth of MLS cells, suggesting that increased expression of PAI-1 by miR-486 repression is critical for survival of MLS cells. Collectively, these results suggest a novel essential molecular mechanism that TLS-CHOP activates PAI-1 expression by repression of miR-486 expression in MLS tumorigenesis and development.Biochemical and Biophysical Research Communications 09/2012; 427(2):355-60. · 2.48 Impact Factor -
Article: Identification of a novel role of Septin 10 in paclitaxel-resistance in cancers through a functional genomics screen.
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ABSTRACT: Paclitaxel (also known as taxol) is a member of the taxane class of anticancer agents, which has a well-known mechanism that blocks cell mitosis and kills tumor cells, that is often used in clinics to treat cancer. However, some carcinomas such as breast, ovarian and non-small-cell lung cancers are often resistant to paclitaxel treatment. In this study, we used a lentiviral siRNA library against the entire human genomes to identify genes associated with sensitivity to paclitaxel. We isolated two paclitaxel-resistant clones carrying the siRNA specific to septin 10 (SEPT10) and to budding uninhibited by benzimidazoles 3. The relation of budding uninhibited by benzimidazoles 3 to paclitaxel sensitivity has already been established, but that of SEPT10 remains unknown. Interestingly, overexpression of SEPT10 increased cells' sensitivity to paclitaxel; we also found that SEPT10 is an important regulator for microtubule stability. Furthermore, we found that paclitaxel-resistant tumors had decreased expression of SEPT10. Thus, SEPT10 may be a novel candidate molecule that acts as a good indicator of paclitaxel-resistant carcinomas.Cancer Science 02/2012; 103(4):821-7. · 3.33 Impact Factor -
Article: Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development.
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ABSTRACT: MicroRNAs (miRNAs) belong to a class of the endogenously expressed non-coding small RNAs which primarily function as gene regulators. Growing evidence suggests that miRNAs have a significant role in tumor development and may constitute robust biomarkers for cancer diagnosis and prognosis. The miR-17-92 cluster especially is markedly overexpressed in several cancers, and is associated with the cancer development and progression. In this study, we have demonstrated that miR-92a is highly expressed in hepatocellular carcinoma (HCC). In addition, the proliferation of HCC-derived cell lines was enhanced by miR-92a and inhibited by the anti-miR-92a antagomir. On the other hand, we have found that the relative amount of miR-92a in the plasmas from HCC patients is decreased compared with that from the healthy donors. Interestingly, the amount of miR-92a was elevated after surgical treatment. Thus, although the physiological significance of the decrease of miR-92a in plasma is still unknown, deregulation of miR-92 expression in cells and plasma should be implicated in the development of HCC.Pathology International 05/2010; 60(5):351-7. · 1.62 Impact Factor -
Article: USP15 plays an essential role for caspase-3 activation during Paclitaxel-induced apoptosis.
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ABSTRACT: Paclitaxel (also known as Taxol) is a well-known anticancer agent that blocks cell mitosis and kills tumor cells, and is often used in clinic to treat cancers. Despite the success of Paclitaxel, the development of drug resistance prevents its clinical applicability. Here, we screened an siRNA library against the entire human genomes using HeLa cells, and have find that lack of USP15 (ubiquitin-specific protease 15) causes Paclitaxel resistance. We also observed the decreased expression of USP15 in Paclitaxel-resistant human ovarian cancer samples. In addition, we have demonstrated that USP15 plays an essential role for stability and activity of caspase-3 during Paclitaxel-induced apoptosis. Thus, USP15 may be a candidate diagnostic marker and therapeutic target for Paclitaxel-resistant cancers.Biochemical and Biophysical Research Communications 09/2009; 388(2):366-71. · 2.48 Impact Factor -
Article: Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients.
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ABSTRACT: MicroRNAs are a family of 19- to 25-nucleotides noncoding small RNAs that primarily function as gene regulators. Aberrant microRNA expression has been described for several human malignancies, and this new class of small regulatory RNAs has both oncogenic and tumor suppressor functions. Despite this knowledge, there is little information regarding microRNAs in plasma especially because microRNAs in plasma, if exist, were thought to be digested by RNase. Recent studies, however, have revealed that microRNAs exist and escape digestion in plasma. We performed microRNA microaray to obtain insight into microRNA deregulation in the plasma of a leukemia patient. We have revealed that microRNA-638 (miR-638) is stably present in human plasmas, and microRNA-92a (miR-92a) dramatically decreased in the plasmas of acute leukemia patients. Especially, the ratio of miR-92a/miR-638 in plasma was very useful for distinguishing leukemia patients from healthy body. The ratio of miR-92a/miR-638 in plasma has strong potential for clinical application as a novel biomarker for detection of leukemia.PLoS ONE 02/2009; 4(5):e5532. · 4.09 Impact Factor -
Article: Effects of dioxin on vascular endothelial growth factor (VEGF) production in the retina associated with choroidal neovascularization.
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ABSTRACT: Cigarette smoking is the most consistent risk factor for age-related macular degeneration (AMD), especially the choroidal neovascularization (CNV)-mediated exudative type. Dioxins and dioxin-like compounds have various effects on living organisms and are also contained in cigarette smoke. However, the effects of dioxins on the eye remain elusive. In this study, the authors examined the association between dioxins and neovascularization in the eye. C57BL/6 mice were injected intraperitoneally with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every other day for 14 days. Messenger RNA expression of cytochrome P450 (CYP)1A1, CYP1B1, vascular endothelial growth factor (VEGF)-A and VEGF-B, and VEGF production were examined in the eyes of TCDD-treated mice and in human retinal pigment epithelial cell lines (ARPE-19) exposed to TCDD. In addition, CNV was induced by photocoagulation in mice injected with TCDD, and the volume of CNV was compared by fluorescence-labeled choroidal flat mount. TCDD injected intraperitoneally increased CYP1A1 mRNA expression in the iris/ciliary body and retina, indicating that TCDD acts directly on ocular tissues through the aryl hydrocarbon receptor (AhR) to promote the transcription of target genes. TCDD also promoted VEGF-A mRNA expression in the retina and the retinal pigment epithelium. TCDD-induced VEGF production at the molecular level was also observed in vivo by immunohistochemistry and in vitro using ARPE-19. Moreover, the injection of TCDD significantly exacerbated photocoagulation-induced CNV in mice. The authors demonstrate that dioxins are among the factors inducing abnormal vascularization in the eye through VEGF production mediated by AhR signaling.Investigative ophthalmology & visual science 02/2009; 50(7):3410-6. · 3.43 Impact Factor -
Article: Heterochromatin protein 1gamma epigenetically regulates cell differentiation and exhibits potential as a therapeutic target for various types of cancers.
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ABSTRACT: Heterochromatin protein 1 (HP1) is a chromosomal protein that participates in both chromatin packaging and gene silencing. Three HP1 isoforms (alpha, beta, and gamma) occur in mammals, but their functional differences are still incompletely understood. In this study, we found that HP1gamma levels are decreased during adipocyte differentiation, whereas HP1alpha and beta levels are expressed constitutively during adipogenesis in cultured preadipocyte cells. In addition, ectopic overexpression of HP1gamma inhibited adipogenesis. Furthermore, we did not detect any HP1gamma protein in the differentiated cells of various normal human tissues. These results suggest that the loss of HP1gamma is required for cell differentiation to occur. On the other hand, the methylation levels of lysine 20 (K20) on histone H4 showed a significant correlation with HP1gamma expression in both these preadipocyte cells and normal tissue samples. However, all cancer tissues examined were positive for HP1gamma but were often negative for trimethylated histone H4 K20. Thus, a dissociation of the correlation between HP1gamma expression and histone H4 K20 trimethylation may reflect the malfunction of epigenetic control. Finally, suppression of HP1gamma expression restrained cell growth in various cancer-derived cell lines, suggesting that HP1gamma may be an effective target for gene therapy against various human cancers. Taken together, our results demonstrate the novel function of HP1gamma in the epigenetic regulation of both cell differentiation and cancer development.American Journal Of Pathology 01/2009; 174(1):309-16. · 4.89 Impact Factor -
Article: USP15 plays an essential role for caspase-3 activation during Paclitaxel-induced apoptosis
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ABSTRACT: a b s t r a c t Paclitaxel (also known as Taxol) is a well-known anticancer agent that blocks cell mitosis and kills tumor cells, and is often used in clinic to treat cancers. Despite the success of Paclitaxel, the development of drug resistance prevents its clinical applicability. Here, we screened an siRNA library against the entire human genomes using HeLa cells, and have find that lack of USP15 (ubiquitin-specific protease 15) causes Pac-litaxel resistance. We also observed the decreased expression of USP15 in Paclitaxel-resistant human ovarian cancer samples. In addition, we have demonstrated that USP15 plays an essential role for stability and activity of caspase-3 during Paclitaxel-induced apoptosis. Thus, USP15 may be a candidate diagnostic marker and therapeutic target for Paclitaxel-resistant cancers. Ó 2009 Elsevier Inc. All rights reserved. Paclitaxel (also known as Taxol) is one of the most effective microtubule-targeting drugs for cancer treatment, and leads to the significant improvements in the survival of patients with many solid tumors including ovarian, breast, prostate, and non-small-cell lung cancers. Paclitaxel disrupts microtubule dynamics by promoting tubulin polymerization and stability, which leads to cell cycle arrest at the G2/M phase, activates mitotic spindle ''checkpoint," and results in apoptotic cell death [1–8]. However, despite a remarkable response of initial treatment with Paclit-axel, progressive diseases eventually develop in some patients. Paclitaxel resistance is a major obstacle that severely limited the improvement of response and survival in Paclitaxel-treated cancer patients [9–13]. Therefore, understanding of the molecu-lar mechanisms contributing to drug resistance may provide us with the opportunity to develop more effective anticancer therapies. Ubiquitin-mediated proteolysis system targets substrates to the 26S proteasome by attaching a polyubiquitin chain to lysine residues in target proteins [14]. The ubiquitin transfer reaction involves three enzymes: the ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). E3 ubiquitin ligases were classified into several types such as the single-subunit RING-finger type, the multi-subunit RING-finger type and the HECT domain type [15]. The best characterized mammalian multi-subunit RING-finger type of E3 is the SCF (Skp1-CUL1-F-box) complex. Each of the SCF complexes is com-posed of a modular E3 core containing RBX1 (also called ROC1) and CUL1, and a substrate specificity module composed of Skp1 and a member of the F-box family of proteins [16]. CUL1 serves as a scaffold and interacts with RBX1 at its carboxyl terminus to re-cruit ubiquitin-conjugated E2, while the amino terminus of CUL1 interacts with Skp1 [16]. F-box proteins bind to Skp1 through its F-box domain and to substrates through its tryptophan and aspar-tic acid (WD) or leucine-rich repeats (LRR) domain [17,18]. F-box proteins determine the substrate specificity of the SCF complex. The large number of F-box proteins found in the human genome suggests that SCF E3 Ub ligases would play a major role in the reg-ulation of a variety of biologic processes [19,20]. On the other hand, these activities are counteracted by a diverse group of deubiquiti-nating enzymes (DUBs), which disassemble and process ubiquitin intermediates [21]. USP15 belongs to the large group of ubiqui-tin-specific processing proteases (USPs) responsible for processing of inactive ubiquitin precursors, removing ubiquitin from cellular adducts and ubiquitinated proteins, and keeping the 26S protea-some free of inhibitory ubiquitin chains [22–26]. Here, we have identified the USP15 gene as a Paclitaxel sensitiv-ity-related gene in HeLa cells using Human 50 K Lentiviral siRNA library. In addition, we have demonstrated that USP15 is required for activation of caspase-3 during Paclitaxel-induced apoptosis. The hallmarks of USP15 may be a candidate for cancer therapeutic method in some types of Paclitaxel-resistant cancers.Biochemical and Biophysical Research Communications 01/2009; 388:366--371. · 2.48 Impact Factor -
Article: Expression of various types of alternatively spliced WAPL transcripts in human cervical epithelia.
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ABSTRACT: We have previously identified a novel gene WAPL that is inducible by human papillomavirus (HPV) E6 and E7 oncoproteins, and is associated with uterine cervical carcinogenesis. A WAPL splice variant named Friend of EBNA2 (FOE) has also been characterized as a binding partner of the Epstein-Barr virus transformation-related protein EBNA2. On the other hand, recent studies have revealed that WAPL is a cohesin-binding protein and promotes sister-chromatid resolution in mitotic prophase. These data demonstrate that WAPL plays an important role in tumorigenesis and cell cycle progression. In this study, we have isolated a large number of additional alternatively spliced WAPL variants from various cervical epithelia. Each variant consists of a variable 5'-terminal region and the conserved remainder. In addition, we have confirmed the genomic organization of the 5'-region of the WAPL gene, and have investigated the characteristic features of the WAPL variants and their products. Furthermore, we have determined the HPV types of the expressed E6/E7 transcripts in the cervical epithelia with a novel PCR protocol. These results should shed light on a novel aspect of WAPL function.Gene 11/2008; 423(1):57-62. · 2.34 Impact Factor -
Article: Dioxin interferes in chromosomal positioning through the aryl hydrocarbon receptor.
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ABSTRACT: Each chromosome occupies its own-specific space called a 'territory' within the interphase nucleus, and the arrangement of chromosome territories (CTs) is important in epigenetic mechanisms. The molecular mechanism to determine the positioning of CTs, however, remains unknown. On the other hand, dioxin is known to be the typical environmental pollutant that affects a wide variety of biological events in many species. Here, we show that dioxin enlarges the minimum distance between chromosome 12 and chromosome 16 territories in human preadipocyte cells, and the alteration of chromosome positioning is canceled by an aryl hydrocarbon receptor (AhR) antagonist alpha-naphthoflavone. Thus, AhR may be a key molecule to regulate chromosome positioning. Our results suggest a novel effect of dioxin toxicity, and demonstrate a clue to reveal the novel molecular mechanism for the arrangement of CTs.Biochemical and Biophysical Research Communications 09/2008; 374(2):361-4. · 2.48 Impact Factor -
Article: Unscheduled overexpression of human WAPL promotes chromosomal instability.
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ABSTRACT: Previously, we have isolated and characterized a novel human gene termed human WAPL that has the characteristics of an oncogene in uterine cervical cancer. WAPL is inducible by human papillomavirus (HPV) E6 and E7 oncoproteins. On the other hand, recent studies have revealed that WAPL regulates sister chromatid resolution by controlling the association of cohesin and chromatin. However, the effects of WAPL overexpression on cervical carcinogenesis are still unclear. Here, we show that WAPL overexpression induces generation of multinucleated cells. In addition, WAPL-overexpressing cells demonstrated increases in chromatid breaks in comparison with control cells. These results were obtained even in HPV-negative cell lines. High frequent premature sister separation by disregulation of cohesin may lead to these results. Thus, our study suggests that unscheduled overexpression of WAPL disturbs mitosis and cytokinesis, and contributes to tumor progression by induction of chromosomal instability (CIN).Biochemical and Biophysical Research Communications 06/2007; 356(3):699-704. · 2.48 Impact Factor -
Article: Correlation between liver metastasis of the colocalization of actin‐related protein 2 and 3 complex and WAVE2 in colorectal carcinoma
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ABSTRACT: Directed movement of normal cells occurs when actin-related protein 2 and 3 complex (Arp2/3 complex) triggers the actin polymerization that forms lamellipodia immediately after binding to WAVE2. In order to determine whether the same mechanism correlates with liver metastasis from colorectal cancer, paired mirror sections of 154 cancer specimens (29 cases with liver metastasis and 125 cases without liver metastasis in which T factor, gender, primary tumor site, and age at operation were matched) were examined immunohistochemically for the localization of Arp2 and WAVE2. Expression of both Arp2 and WAVE2 was detected in the same cancer cells in 55 (35.7%) of the 154 cases, but not detected in the normal colonic epithelial cells. Univariate analysis showed that the colocalization was significantly predictive of liver metastasis (risk ratio [RR] 8.760. Likewise, histological grade (RR 2.46), lymphatic invasion (RR 9.95), and tumor budding (RR 4.00) were significant predictors. Among these, colocalization and lymphatic invasion were shown to be independent risk factors by multivariate analysis. Another 59 colorectal specimens were examined for mRNA expression of Arp2 by real time polymerase chain reaction. High mRNA levels of Arp2, that in situ hybridization revealed to be expressed by the cancer cells, were significantly associated with liver metastasis. However, its effect was absorbed by the influence of risk of the colocalization that is closely related to high expression of Arp2. These results indicate that the colocalization of Arp2 and WAVE2 is an independent risk factor for liver metastasis of colorectal carcinoma. (Cancer Sci 2007; 98: 992–999)Cancer Science 04/2007; 98(7):992 - 999. · 3.33 Impact Factor -
Article: Generation of the novel monoclonal antibody against TLS/EWS-CHOP chimeric oncoproteins that is applicable to one of the most sensitive assays for myxoid and round cell liposarcomas.
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ABSTRACT: The fusion oncoproteins, TLS-CHOP and EWS-CHOP, are characteristic markers for myxoid and round cell liposarcomas (MLS/RCLS). Especially, the peptide sequence of 26 amino acids corresponding to the normally untranslated CHOP exon 2 and parts of exon 3 (5'-UTR) is a unique structure for these chimeric proteins. In this report, we have generated monoclonal antibodies against the unique peptide sequence of TLS/EWS-CHOP oncoproteins. These antibodies reacted with TLS-CHOP fusion protein, but not reacted with normal TLS and CHOP proteins by Western blot analysis. In addition, one of the antibodies also recognized the chimeric oncoprotein in archival paraffin-embedded tissue samples of MLS/RCLS. The oncoprotein was detectable by the antibody even in the paraffin-embedded tissue samples whose mRNAs were too degraded to be detected by a nested reverse transcription-polymerase chain reaction-based assay. Thus, the molecular assay using the novel antibody is expected to be one of the most sensitive diagnostic assays for MLS/RCLS.American Journal of Surgical Pathology 04/2006; 30(3):351-6. · 4.35 Impact Factor -
Article: Detection of fusion genes in sarcomas using paraffin-embedded tissues.
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ABSTRACT: Many sarcomas are characterized by specific recurrent chromosomal translocations resulting in gene fusions. The genes involved in almost all of these translocations have been cloned, greatly changing sarcoma diagnosis. At the biological level, these chromosomal translocations produce highly specific fusion genes that encode key molecules for tumor development. The clinical correlation between these translocation-derived genetic markers and discrete histopathological entities has been remarkable. Today, detection of fusion genes plays a crucial role in the diagnosis of sarcomas that harbor atypical clinical or pathological presentations. The focus of this brief review is the recent impact that cytogenetic and molecular detection of these translocations has had on sarcoma diagnosis using paraffin-embedded sections.Neuropathology 10/2005; 25(3):263-8. · 2.02 Impact Factor -
Article: Effects of 3-methylcholanthrene on the transcriptional activity and mRNA accumulation of the oncogene hWAPL.
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ABSTRACT: hWAPL is a human oncogene associated with uterine cervical cancer. Here, we demonstrate that hWAPL transcription is induced by 3-methylcholanthrene (3-MC) in the cervical carcinoma-derived cell line SiHa. hWAPL transcription was analyzed with evaluation of the mRNA and heterogeneous nuclear RNA (hnRNA) levels by quantitative real time PCR analysis. Flow cytometric analysis suggested that the alteration of hWAPL mRNA levels is independent of cell cycle profile. We also found that DMSO and some components of FBS affect hWAPL transcription. Interestingly, when the aryl hydrocarbon receptor (AhR) function was inhibited by alpha-naphthoflavone (ANF), the induction of hWAPL transcription by 3-MC was greater than that in AhR-functioning normal cells. These observations suggest that there are complex mechanisms regulating the transcription of hWAPL. Furthermore, mRNA level of a mouse homolog of hWAPL in mouse uterus was induced by 3-MC injection into the abdominal cavity. Thus, some effects from 3-MC exposure on uterus may be mediated by the unscheduled overexpression of hWAPL.Cancer Letters 05/2005; 221(1):21-8. · 4.24 Impact Factor -
Article: A dioxin sensitive gene, mammalian WAPL, is implicated in spermatogenesis.
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ABSTRACT: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disruptor that produces a variety of toxic effects. We have isolated a mouse homolog of the hWAPL gene, termed mouse WAPL (mWAPL), as a target of TCDD by cDNA representational difference analysis from mouse embryonic stem cells. A statistically significant increase in mWAPL expression was observed at 0.1 microM TCDD in AhR-/- mouse embryonic fibroblast cells. Interestingly, at 1 microM TCDD, mWAPL mRNA levels decreased in AhR+/+ cells, but further increased in AhR-/- cells. hWAPL and mWAPL were highly expressed only in testes among normal tissue samples, and we observed mWAPL localization in the synaptonemal complex of testicular chromosomes. In addition, mouse testes decreased the expression of mWAPL mRNA after a single intraperitoneal injection of TCDD. Thus, mammalian WAPL such as hWAPL and mWAPL may be involved in spermatogenesis and be target genes mediating the reproductive toxicity induced by TCDD.FEBS Letters 02/2005; 579(1):167-72. · 3.54 Impact Factor -
Article: Alteration of chromosome positioning during adipocyte differentiation.
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ABSTRACT: Chromosomes are highly restricted to specific chromosome territories within the interphase nucleus. The arrangement of chromosome territories is non-random, exhibiting a defined radial distribution as well as a preferential association with specific nuclear compartments, which indicates a functional role for chromosome-territory organization in the regulation of gene expression. In this report, we focus on changes in adipocyte differentiation that are related to a specific chromosomal translocation associated with liposarcoma tumorigenesis, t(12;16). We have examined the relative and radial positioning of the chromosome territories of human chromosomes 12 and 16 during adipocyte differentiation, and detected a close association between the territories of chromosomes 12 and 16 in differentiated adipocytes, an association not observed in preadipocytes. Although further studies are required to elucidate the underlying reasons for the adipocyte-specific translocation of chromosomes 12 and 16, our observations indicate that alteration of relative chromosome positioning might play a key role in the tumorigenesis of human liposarcomas. In addition, these results demonstrate the potential impact of higher order chromatin organization on the epigenetic mechanisms that control gene expression and gene silencing during cell differentiation.Journal of Cell Science 11/2004; 117(Pt 24):5897-903. · 6.11 Impact Factor -
Article: Expression of a novel human gene, human wings apart-like (hWAPL), is associated with cervical carcinogenesis and tumor progression.
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ABSTRACT: In Drosophila melanogaster, the wings apart-like (wapl) gene encodes a protein that regulates heterochromatin structure. Here, we characterize a novel human homologue of wapl (termed human WAPL; hWAPL). The hWAPL mRNA was predominantly expressed in uterine cervical cancer, with weak expression in all other normal and tumor tissues examined. hWAPL expression in benign epithelia was confined to the basal cell layers, whereas in dysplasias it increasingly appeared in more superficial cell layers and showed a significant correlation with severity of dysplasia. Diffuse hWAPL expression was found in all invasive squamous cell carcinomas examined. In addition, NIH3T3 cells overexpressing hWAPL developed into tumors on injection into nude mice. Furthermore, repression of hWAPL expression by RNA interference induced cell death in SiHa cells. These results demonstrate that hWAPL is associated with cell growth, and the hWAPL expression may play a significant role in cervical carcinogenesis and tumor progression.Cancer Research 06/2004; 64(10):3545-9. · 7.86 Impact Factor -
Article: Increased expression of IgE-dependent histamine-releasing factor in endometriotic implants.
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ABSTRACT: A complex network of cytokines mediates the immunoregulatory responses leading to endometriosis. Recent intensive studies suggest that monocyte and T cell chemoattractants contribute to the inflammatory environment of endometriotic implants. The relationship between the inflammation present during endometriosis and the development of endometriotic implants in the peritoneal cavity remains unclear. On the other hand, the association between endometriosis and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) exposure has been discussed in recent years, and our previous results revealed that IgE-dependent histamine-releasing factor (HRF) is inducible by TCDD. The present study aimed to clarify the expression, localization, and function of HRF in endometriosis. Northern blot analysis demonstrated that HRF is overexpressed in endometriotic implants. RT-PCR with Southern blot analysis, however, showed that HRF overexpression was not always accompanied by CYP1A1 induction in endometriotic implants, suggesting that HRF is inducible in endometriosis without exposure to TCDD. HRF is also inducible by macrophage colony-stimulating factor (M-CSF). Immunohistochemistry showed CD68-positive macrophages in the stroma of endometriotic implants, adjacent to regions with prominent HRF accumulation. HRF-overexpressing cells exhibited high implantation efficiency in comparison to control cells when the cells were injected into the peritoneal cavities of nude mice. These results suggest that the accumulation of macrophages in endometriotic implants induces HRF; the overexpression of HRF accelerates the growth of endometriotic implants.The Journal of Pathology 04/2003; 199(3):318-23. · 6.32 Impact Factor -
Article: TLS-CHOP target gene DOL54 expression in liposarcomas and malignant fibrous histiocytomas.
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ABSTRACT: Downstream of the gene for the liposarcoma-associated fusion oncoprotein 54 (DOL54) is a target gene of the myxoid liposarcoma and round cell liposarcoma (M-LPS/RC-LPS) oncogene, TLS/FUS-CHOP. The DOL54 gene product is closely associated with adipogenic differentiation. DOL54 overexpression resulted in tumorigenicity when Chinese Hamster Ovary (CHO) cells were injected subcutaneously into nude mice. The biological significance of DOL54 expression for human malignant soft tissue tumors, however, has not yet been investigated. We examined TLS-CHOP and DOL54 expression in M-LPS/RC-LPS, well-differentiated liposarcoma and malignant fibrous histiocytoma (MFH), a tumor whose cellular origin has not been determined. We observed DOL54 expression in 50% of M-LPS/RC-LPS cases (in which TLS-CHOP was also expressed) and 33% of MFH cases, suggesting that a portion of MFH lesions may either derive from adipocytic precursor cells or have the potential to undergo adipogenic differentiation. In this manner, M-LPS/RC-LPS and MFH lesions may share tumorigenic characteristics, resulting from the unscheduled expression of DOL54.Pathology International 09/2002; 52(8):497-500. · 1.62 Impact Factor
Top Journals
Institutions
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2002–2012
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Tokyo Medical University
- • Department of Molecular Pathology
- • Department of Pathology
Tokyo, Tokyo-to, Japan
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