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http://purl.uniprot.org/citations/15289334http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15289334http://www.w3.org/2000/01/rdf-schema#comment"Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been shown to stimulate the growth of a variety of cells in an autocrine or paracrine manner. Although HB-EGF is widely expressed in tumors compared with normal tissue, its contribution to tumorigenicity is unknown. HB-EGF can be produced as a membrane-anchored form (pro-HB-EGF) and later processed to a soluble form (s-HB-EGF), although a significant amount of pro-HB-EGF remains uncleaved on the cell surface. To understand the roles of two forms of HB-EGF in promoting tumor growth, we have studied the effects of HB-EGF expression in the process of tumorigenesis using in vitro and in vivo systems. We demonstrate here that in EJ human bladder cancer cells containing a tetracycline-regulatable s-HB-EGF or pro-HB-EGF expression system, s-HB-EGF expression increased their transformed phenotypes, including growth rate, colony-forming ability, and activation of cyclin D1 promoter, as well as induction of vascular endothelial growth factor in vitro. Moreover, s-HB-EGF or wild-type HB-EGF induced the expression and activities of the metalloproteases, MMP-9 and MMP-3, leading to enhanced cell migration. In vivo studies also demonstrated that tumor cells expressing s-HB-EGF or wild-type HB-EGF significantly enhanced tumorigenic potential in athymic nude mice and exerted an angiogenic effect, increasing the density and size of tumor blood vessels. However, cells expressing solely pro-HB-EGF did not exhibit any significant tumorigenic potential. These findings establish s-HB-EGF as a potent inducer of tumor growth and angiogenesis and suggest that therapeutic intervention aimed at the inhibition of s-HB-EGF functions may be useful in cancer treatment."xsd:string
http://purl.uniprot.org/citations/15289334http://purl.org/dc/terms/identifier"doi:10.1158/0008-5472.can-04-0925"xsd:string
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/author"Fang L."xsd:string
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/author"Lee S.W."xsd:string
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/author"Taniguchi N."xsd:string
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/author"Higashiyama S."xsd:string
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/author"Ongusaha P.P."xsd:string
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/author"Macip S."xsd:string
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/author"Kwak J.C."xsd:string
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/author"Zwible A.J."xsd:string
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/name"Cancer Res"xsd:string
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/pages"5283-5290"xsd:string
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/title"HB-EGF is a potent inducer of tumor growth and angiogenesis."xsd:string
http://purl.uniprot.org/citations/15289334http://purl.uniprot.org/core/volume"64"xsd:string
http://purl.uniprot.org/citations/15289334http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15289334
http://purl.uniprot.org/citations/15289334http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15289334
http://purl.uniprot.org/uniprot/Q06186#attribution-A089DE4D09F700C7A56E75CC1DA564F3http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/15289334
http://purl.uniprot.org/uniprot/#_Q53H93-mappedCitation-15289334http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15289334
http://purl.uniprot.org/uniprot/#_Q06186-mappedCitation-15289334http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15289334
http://purl.uniprot.org/uniprot/#_Q14486-mappedCitation-15289334http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15289334
http://purl.uniprot.org/uniprot/#_Q14487-mappedCitation-15289334http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15289334
http://purl.uniprot.org/uniprot/#_Q5FW64-mappedCitation-15289334http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15289334
http://purl.uniprot.org/uniprot/#_Q99075-mappedCitation-15289334http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15289334