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Med.\n            <jats:bold>7:<\/jats:bold>\n            350-355, 2001). EBNA3C can reverse the ability of Nm23-H1 to suppress migration of Burkitt's lymphoma and breast carcinoma cell lines in vitro. EBNA3C contributes to EBV-associated human cancers by regulating transcription of a number of cellular and viral promoters and by targeting and altering the transcription activities of the metastasis suppressor Nm23-H1. Cyclo-oxygenase-2 (COX-2), an inducible enzyme important in inflammation, is overexpressed in a variety of cancers and can influence cell migration. In this report we show that Nm23-H1 and EBNA3C can modulate expression of COX-2 in the context of EBV infection and transformation. The levels of COX-2 were consistently higher in EBV-positive cells than in EBV-negative cells. Additionally, we show that Nm23-H1 can upregulate the COX-2 promoter element in luciferase reporter assays, whereas EBNA3C alone did not affect the level of response but clearly contributed to an additive increase when coexpressed with Nm23-H1. The downstream effect of COX-2 expression was also evaluated and showed that prostaglandin E\n            <jats:sub>2<\/jats:sub>\n            levels increased with Nm23-H1 and that there was some level of cooperativity in the presence of EBNA3C. The majority of this response was mediated through the cyclic AMP response element and NF-\u03baB sites. These studies suggest a potential role for COX-2 in EBV-associated human cancers.\n          <\/jats:p>","DOI":"10.1128\/jvi.80.3.1321-1331.2006","type":"journal-article","created":{"date-parts":[[2006,1,13]],"date-time":"2006-01-13T13:18:00Z","timestamp":1137158280000},"page":"1321-1331","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Epstein-Barr Virus Protein Can Upregulate Cyclo-Oxygenase-2 Expression through Association with the Suppressor of Metastasis Nm23-H1"],"prefix":"10.1128","volume":"80","author":[{"given":"Rajeev","family":"Kaul","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Medicine, and Tumor Virology Program, Abramson Comprehensive Cancer Center, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhash C.","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Medicine, and Tumor Virology Program, Abramson Comprehensive Cancer Center, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanao","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Medicine, and Tumor Virology Program, Abramson Comprehensive Cancer Center, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Medicine, and Tumor Virology Program, Abramson Comprehensive Cancer Center, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tathagata","family":"Choudhuri","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Medicine, and Tumor Virology Program, Abramson Comprehensive Cancer Center, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erle S.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Medicine, and Tumor Virology Program, Abramson Comprehensive Cancer Center, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.6.3491-3498.1994"},{"key":"e_1_3_2_3_2","first-page":"728","volume":"63","year":"2003","unstructured":"Araki, Y., S. 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