Gene expression profiles in human gastric cancer: expression of maspin correlates with lymph node metastasis

Terashima, Masanori; Maesawa, Chihaya; Oyama, Kenichi; Ohtani, S.; Akiyama, Yuji; Ogasawara, Satoshi; Takagane, Akinori; Saito, Kazuyoshi; Masuda, Tomoyuki; Kanzaki, Norio; Matsuyama, Shin-ichi; Hoshino, Yutaka; Kogure, Michihiko; Gotoh, Mitsukazu; Shirane, Masatoshi; Mori, Koichiro

doi:10.1038/sj.bjc.6602429

Cited by 48 publications

(30 citation statements)

References 27 publications

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“…Maspin is a serine protease inhibitor (also called serpin B5) involved in cell adhesion, motility, apoptosis, and angiogenesis (29). It is usually considered to be a tumor suppressor (4) but has been reported to both inhibit and increase metastatic potential in different systems (43,50). By Western blotting, we confirmed the nuclear enrichment of maspin in NPC cells stably and transiently expressing EBNA1, as well as decreased nuclear levels upon EBNA1 silencing.…”

Section: Discussionsupporting

confidence: 60%

Changes in the Nasopharyngeal Carcinoma Nuclear Proteome Induced by the EBNA1 Protein of Epstein-Barr Virus Reveal Potential Roles for EBNA1 in Metastasis and Oxidative Stress Responses

Cao

Mansouri

Frappier

2012

J Virol

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Epstein-Barr virus (EBV) infection is causatively associated with a variety of human cancers, including nasopharyngeal carcinoma (NPC).The only viral nuclear protein expressed in NPC is EBNA1, which can alter cellular properties in ways that may promote oncogenesis. Here, we used 2-dimensional difference gel electrophoresis (2-D DiGE) to profile changes in the nuclear proteome that occur after stable expression of EBNA1 in the EBV-negative NPC cell line CNE2. We found that EBNA1 consistently altered the levels of a small percentage of the nuclear proteins. The identification of 19 of these proteins by mass spectrometry revealed that EBNA1 upregulated three proteins affecting metastatic potential (stathmin 1, maspin, and Nm23-H1) and several proteins in the oxidative stress response pathway, including the antioxidants superoxide dismutase 1 (SOD1) and peroxiredoxin 1 (Prx1). Western blot analysis verified that EBNA1 expression upregulated and EBNA1 silencing downregulated these proteins. In addition, transcripts for stathmin 1 were induced by EBNA1, whereas EBNA1 only affected Prx1 and SOD1 at the protein level. Further investigation of the EBNA1 effects on the redox pathway showed that long-term EBNA1 expression in NPC resulted in increased reactive oxygen species (ROS) and increased levels of the NADPH oxidases NOX1 and NOX2, known to generate ROS. In addition, EBNA1 depletion in EBV-positive cells decreased NOX2 and ROS. The results show multiple roles for EBNA1 in the oxidative stress response pathway and suggest mechanisms by which EBNA1 may promote NPC metastases. E pstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus that is harbored in at least 90% of the world population (40). Transmitted through saliva, EBV infects B lymphocytes as well as the epithelium of the orthopharynx. Upon primary infection, EBV immediately establishes latent infection in cells by maintaining multiple copies of its genome in the form of episomes. While most infected individuals control the virus efficiently and remain free of EBV-associated diseases, latent EBV infection is linked to the development of both lymphoid and epithelial tumors. Nasopharyngeal carcinoma (NPC) is one such epithelial tumor in which EBV is widely recognized as a causative agent, since most NPC tumors are monoclonal proliferations of latently EBV-infected cells (38). These tumor cells express only one EBV nuclear protein, EBNA1, in addition to the EBV latent membrane proteins LMP1 and LMP2 (38).Epstein-Barr nuclear antigen 1 (EBNA1) is essential for the establishment of latent EBV infection since it replicates and segregates the viral genome in proliferating cells (reviewed in reference 17). Additionally, it is a transcriptional activator for other EBV latency genes. Aside from its roles in viral persistence, increasing numbers of observations suggest that EBNA1 alters cellular processes in ways that contribute to host cell survival and proliferation. First, EBNA1 is expressed in all latency forms in proliferating cells and is the only EBV protein...

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Section: Discussionsupporting

confidence: 60%

Changes in the Nasopharyngeal Carcinoma Nuclear Proteome Induced by the EBNA1 Protein of Epstein-Barr Virus Reveal Potential Roles for EBNA1 in Metastasis and Oxidative Stress Responses

Cao

Mansouri

Frappier

2012

J Virol

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“…SERPINB5 regulates the invasive activity of tumor cells (35), inhibits angiogenesis (36), primary tumor growth as well as invasion and metastasis (37). However, high expression of maspin is associated with early tumor relapse in breast cancer (38), and SERPINB5 may contribute to gastric carcinogenesis and have a potential role in tumor metastasis in GC (39,40). Our microarray data, real-time PCR and IHC assay demonstrated that the expression of SERPINB5 was up-regulated at the RNA and protein levels in the GC tissues.…”

Section: Discussionmentioning

confidence: 77%

Development of a survival prediction model for gastric cancer using serine proteases and their inhibitors

Lei

Liu

Zhang

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Proteolytic enzymes play a key role in the metastatic stage of gastric cancer (GC). In this study, we aimed to identify the serine proteases (SPs) and their inhibitors (serpins) as related to GC. The gene expression profiles of 40 cases of GC were initially detected by cDNA microarray. The results of the differentially expressed SPs and their inhibitor genes from the microarrays were confirmed by real-time PCR. The status of the immunohistochemical staining of the confirmed genes in patients with complete data was used to develop a survival prediction model. Finally, the prediction model was tested in different groups of GC patients. As a result, seven genes, SERPINB5, KLK10, KLK11, HPN, SPINK1, SERPINA5 and PRSS8, were considered as GC progression-related genes. A survival prediction model including the immunohistochemical scores of three genes and the tumor node metastasis (TNM) score was developed: Survival time (months) = 88.8607 + 2.6395 SERPINB5 -12.0772 KLK10 + 13.7562 KLK11 -7.0318 TNM. In conclusion, SERPINB5, KLK10, KLK11, HPN, SPINK1, SERPINA5 and PRSS8 were GC progression-related SPs or serpin genes. The model consisting of the expression profiles of three genes extracted from the microarray study accompanied by the TNM score accurately predicts surgeryrelated survival of GC patients.

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“…We have previously revealed, using an oligonucleotide microarray, that claudin-4 is upregulated in gastric cancer [6], and another study using an oligonucleotide microarray has reported that claudin-4 is upregulated in intestinal-type gastric cancer [7]. Moreover, claudin-4 is reportedly highly expressed in gastric intestinal-type adenocarcinoma [5,8,9].…”

mentioning

confidence: 99%

Expression of tight-junction-associated proteins in human gastric cancer: downregulation of claudin-4 correlates with tumor aggressiveness and survival

et al. 2009

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Gene expression profiles in human gastric cancer: expression of maspin correlates with lymph node metastasis

Cited by 48 publications

References 27 publications

Changes in the Nasopharyngeal Carcinoma Nuclear Proteome Induced by the EBNA1 Protein of Epstein-Barr Virus Reveal Potential Roles for EBNA1 in Metastasis and Oxidative Stress Responses

Changes in the Nasopharyngeal Carcinoma Nuclear Proteome Induced by the EBNA1 Protein of Epstein-Barr Virus Reveal Potential Roles for EBNA1 in Metastasis and Oxidative Stress Responses

Development of a survival prediction model for gastric cancer using serine proteases and their inhibitors

Expression of tight-junction-associated proteins in human gastric cancer: downregulation of claudin-4 correlates with tumor aggressiveness and survival

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