A Functional Genomics Approach to Kaposi's Sarcoma
: Kaposi's sarcoma (KS) is the most frequent malignancy afflicting acquired immune‐deficiency syndrome (AIDS) patients. Tumor lesions are characterized by spindle cells of vascular origin and vascularization. Kaposi's sarcoma‐associated herpes virus (KSHV) is consistently found in all form...
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| Veröffentlicht in: | Annals of the New York Academy of Sciences 2002-12, Vol.975 (1), p.180-191 |
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| creator | MOSES, ASHLEE V. JARVIS, MICHAEL A. RAGGO, CAMILO BELL, YOLANDA C. RUHL, REBECCA LUUKKONEN, B.G. MATTIAS GRIFFITH, DIANA J. WAIT, CECILY L. DRUKER, BRIAN J. HEINRICH, MICHAEL C. NELSON, JAY A. FRÜH, KLAUS |
| description | : Kaposi's sarcoma (KS) is the most frequent malignancy afflicting acquired immune‐deficiency syndrome (AIDS) patients. Tumor lesions are characterized by spindle cells of vascular origin and vascularization. Kaposi's sarcoma‐associated herpes virus (KSHV) is consistently found in all forms of KS. Infection of dermal microvascular endothelial cells (DMVEC) with KSHV recapitulates spindle cell formation in vitro. We studied this transformation process by DNA microarray analysis comparing the RNA expression profiles of KSHV‐infected and mock‐infected DMVEC. Genes involved in tumorigenesis, angiogenesis, host defense, cell growth and differentiation, transcription, and metabolism were observed to change significantly upon infection with KSHV. One of the most consistently KSHV‐induced genes was the receptor tyrosine kinase and proto‐oncogene c‐Kit. Inhibition of c‐Kit activity with the pharmacological inhibitor of c‐Kit signaling STI571 reversed the KSHV‐induced morphological transformation of DMVEC. Moreover, overexpression studies showed that c‐Kit was sufficient to induce spindle cell formation (Moses et al. J. Virol. 76(16): 8383‐8399). These data demonstrate that microarrays are useful for the identification of pharmacological targets essential for KS tumorigenesis. |
| doi_str_mv | 10.1111/j.1749-6632.2002.tb05951.x |
| format | Article |
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MATTIAS ; GRIFFITH, DIANA J. ; WAIT, CECILY L. ; DRUKER, BRIAN J. ; HEINRICH, MICHAEL C. ; NELSON, JAY A. ; FRÜH, KLAUS</creator><creatorcontrib>MOSES, ASHLEE V. ; JARVIS, MICHAEL A. ; RAGGO, CAMILO ; BELL, YOLANDA C. ; RUHL, REBECCA ; LUUKKONEN, B.G. MATTIAS ; GRIFFITH, DIANA J. ; WAIT, CECILY L. ; DRUKER, BRIAN J. ; HEINRICH, MICHAEL C. ; NELSON, JAY A. ; FRÜH, KLAUS</creatorcontrib><description>: Kaposi's sarcoma (KS) is the most frequent malignancy afflicting acquired immune‐deficiency syndrome (AIDS) patients. Tumor lesions are characterized by spindle cells of vascular origin and vascularization. Kaposi's sarcoma‐associated herpes virus (KSHV) is consistently found in all forms of KS. Infection of dermal microvascular endothelial cells (DMVEC) with KSHV recapitulates spindle cell formation in vitro. We studied this transformation process by DNA microarray analysis comparing the RNA expression profiles of KSHV‐infected and mock‐infected DMVEC. Genes involved in tumorigenesis, angiogenesis, host defense, cell growth and differentiation, transcription, and metabolism were observed to change significantly upon infection with KSHV. One of the most consistently KSHV‐induced genes was the receptor tyrosine kinase and proto‐oncogene c‐Kit. Inhibition of c‐Kit activity with the pharmacological inhibitor of c‐Kit signaling STI571 reversed the KSHV‐induced morphological transformation of DMVEC. Moreover, overexpression studies showed that c‐Kit was sufficient to induce spindle cell formation (Moses et al. J. Virol. 76(16): 8383‐8399). These data demonstrate that microarrays are useful for the identification of pharmacological targets essential for KS tumorigenesis.</description><identifier>ISSN: 0077-8923</identifier><identifier>EISSN: 1749-6632</identifier><identifier>DOI: 10.1111/j.1749-6632.2002.tb05951.x</identifier><identifier>PMID: 12538164</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>antisense ; Benzamides ; c-kit ; Cell Line, Transformed ; Cell Transformation, Neoplastic - drug effects ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Viral - drug effects ; Cell Transformation, Viral - genetics ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - pathology ; Endothelium, Vascular - virology ; Enzyme Inhibitors - pharmacology ; Gene Expression Profiling ; Genomics ; Herpesvirus 8, Human - genetics ; Herpesvirus 8, Human - pathogenicity ; Humans ; Imatinib Mesylate ; Kaposi's sarcoma-associated herpesvirus ; microarray ; Oligonucleotide Array Sequence Analysis ; Piperazines - pharmacology ; Proto-Oncogene Proteins c-kit - genetics ; Pyrimidines - pharmacology ; RNA, Antisense - genetics ; RNA, Antisense - pharmacology ; Sarcoma, Kaposi - etiology ; Sarcoma, Kaposi - genetics ; Virulence - genetics</subject><ispartof>Annals of the New York Academy of Sciences, 2002-12, Vol.975 (1), p.180-191</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4090-c5268279d1d02066511284119b5eea90ec063f26ca031c75111a82738da76b373</citedby><cites>FETCH-LOGICAL-c4090-c5268279d1d02066511284119b5eea90ec063f26ca031c75111a82738da76b373</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1749-6632.2002.tb05951.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1749-6632.2002.tb05951.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12538164$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MOSES, ASHLEE V.</creatorcontrib><creatorcontrib>JARVIS, MICHAEL A.</creatorcontrib><creatorcontrib>RAGGO, CAMILO</creatorcontrib><creatorcontrib>BELL, YOLANDA C.</creatorcontrib><creatorcontrib>RUHL, REBECCA</creatorcontrib><creatorcontrib>LUUKKONEN, B.G. MATTIAS</creatorcontrib><creatorcontrib>GRIFFITH, DIANA J.</creatorcontrib><creatorcontrib>WAIT, CECILY L.</creatorcontrib><creatorcontrib>DRUKER, BRIAN J.</creatorcontrib><creatorcontrib>HEINRICH, MICHAEL C.</creatorcontrib><creatorcontrib>NELSON, JAY A.</creatorcontrib><creatorcontrib>FRÜH, KLAUS</creatorcontrib><title>A Functional Genomics Approach to Kaposi's Sarcoma</title><title>Annals of the New York Academy of Sciences</title><addtitle>Ann N Y Acad Sci</addtitle><description>: Kaposi's sarcoma (KS) is the most frequent malignancy afflicting acquired immune‐deficiency syndrome (AIDS) patients. Tumor lesions are characterized by spindle cells of vascular origin and vascularization. Kaposi's sarcoma‐associated herpes virus (KSHV) is consistently found in all forms of KS. Infection of dermal microvascular endothelial cells (DMVEC) with KSHV recapitulates spindle cell formation in vitro. We studied this transformation process by DNA microarray analysis comparing the RNA expression profiles of KSHV‐infected and mock‐infected DMVEC. Genes involved in tumorigenesis, angiogenesis, host defense, cell growth and differentiation, transcription, and metabolism were observed to change significantly upon infection with KSHV. One of the most consistently KSHV‐induced genes was the receptor tyrosine kinase and proto‐oncogene c‐Kit. Inhibition of c‐Kit activity with the pharmacological inhibitor of c‐Kit signaling STI571 reversed the KSHV‐induced morphological transformation of DMVEC. Moreover, overexpression studies showed that c‐Kit was sufficient to induce spindle cell formation (Moses et al. J. Virol. 76(16): 8383‐8399). These data demonstrate that microarrays are useful for the identification of pharmacological targets essential for KS tumorigenesis.</description><subject>antisense</subject><subject>Benzamides</subject><subject>c-kit</subject><subject>Cell Line, Transformed</subject><subject>Cell Transformation, Neoplastic - drug effects</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Viral - drug effects</subject><subject>Cell Transformation, Viral - genetics</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - pathology</subject><subject>Endothelium, Vascular - virology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Gene Expression Profiling</subject><subject>Genomics</subject><subject>Herpesvirus 8, Human - genetics</subject><subject>Herpesvirus 8, Human - pathogenicity</subject><subject>Humans</subject><subject>Imatinib Mesylate</subject><subject>Kaposi's sarcoma-associated herpesvirus</subject><subject>microarray</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Piperazines - pharmacology</subject><subject>Proto-Oncogene Proteins c-kit - genetics</subject><subject>Pyrimidines - pharmacology</subject><subject>RNA, Antisense - genetics</subject><subject>RNA, Antisense - pharmacology</subject><subject>Sarcoma, Kaposi - etiology</subject><subject>Sarcoma, Kaposi - genetics</subject><subject>Virulence - genetics</subject><issn>0077-8923</issn><issn>1749-6632</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkMFOg0AQhjdGY2v1FQzxoCdwdhd2wYshjaXGWg_VGE-bZdlGKhRkIbZvLwRSz85lDvPNP5MPoSsMDm7rduNg7gY2Y5Q4BIA4dQxe4GFnd4TGh9ExGgNwbvsBoSN0ZswGABPf5adohIlHfczcMSKhNWu2qk6LrcysSG-LPFXGCsuyKqT6tOrCepJlYdIbY61kpYpcnqOTtcyMvhj6BL3NHl6nc3vxEj1Ow4WtXAjAVh5hPuFBghMgwJiHu-sYB7GntQxAK2B0TZiSQLHi7RjLlqd-IjmLKacTdN3ntq98N9rUIk-N0lkmt7pojODEJy7z3Ba860FVFcZUei3KKs1ltRcYRGdMbESnRXRaRGdMDMbErl2-HK40ca6Tv9VBUQvc98BPmun9P6LF8iNcYR_aBLtPSE2td4cEWX0Jxin3xPsyEnQ-4_C8pCKiv9cSh34</recordid><startdate>200212</startdate><enddate>200212</enddate><creator>MOSES, ASHLEE V.</creator><creator>JARVIS, MICHAEL A.</creator><creator>RAGGO, CAMILO</creator><creator>BELL, YOLANDA C.</creator><creator>RUHL, REBECCA</creator><creator>LUUKKONEN, B.G. MATTIAS</creator><creator>GRIFFITH, DIANA J.</creator><creator>WAIT, CECILY L.</creator><creator>DRUKER, BRIAN J.</creator><creator>HEINRICH, MICHAEL C.</creator><creator>NELSON, JAY A.</creator><creator>FRÜH, KLAUS</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200212</creationdate><title>A Functional Genomics Approach to Kaposi's Sarcoma</title><author>MOSES, ASHLEE V. ; JARVIS, MICHAEL A. ; RAGGO, CAMILO ; BELL, YOLANDA C. ; RUHL, REBECCA ; LUUKKONEN, B.G. MATTIAS ; GRIFFITH, DIANA J. ; WAIT, CECILY L. ; DRUKER, BRIAN J. ; HEINRICH, MICHAEL C. ; NELSON, JAY A. ; FRÜH, KLAUS</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4090-c5268279d1d02066511284119b5eea90ec063f26ca031c75111a82738da76b373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>antisense</topic><topic>Benzamides</topic><topic>c-kit</topic><topic>Cell Line, Transformed</topic><topic>Cell Transformation, Neoplastic - drug effects</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Cell Transformation, Viral - drug effects</topic><topic>Cell Transformation, Viral - genetics</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - pathology</topic><topic>Endothelium, Vascular - virology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Gene Expression Profiling</topic><topic>Genomics</topic><topic>Herpesvirus 8, Human - genetics</topic><topic>Herpesvirus 8, Human - pathogenicity</topic><topic>Humans</topic><topic>Imatinib Mesylate</topic><topic>Kaposi's sarcoma-associated herpesvirus</topic><topic>microarray</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Piperazines - pharmacology</topic><topic>Proto-Oncogene Proteins c-kit - genetics</topic><topic>Pyrimidines - pharmacology</topic><topic>RNA, Antisense - genetics</topic><topic>RNA, Antisense - pharmacology</topic><topic>Sarcoma, Kaposi - etiology</topic><topic>Sarcoma, Kaposi - genetics</topic><topic>Virulence - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MOSES, ASHLEE V.</creatorcontrib><creatorcontrib>JARVIS, MICHAEL A.</creatorcontrib><creatorcontrib>RAGGO, CAMILO</creatorcontrib><creatorcontrib>BELL, YOLANDA C.</creatorcontrib><creatorcontrib>RUHL, REBECCA</creatorcontrib><creatorcontrib>LUUKKONEN, B.G. MATTIAS</creatorcontrib><creatorcontrib>GRIFFITH, DIANA J.</creatorcontrib><creatorcontrib>WAIT, CECILY L.</creatorcontrib><creatorcontrib>DRUKER, BRIAN J.</creatorcontrib><creatorcontrib>HEINRICH, MICHAEL C.</creatorcontrib><creatorcontrib>NELSON, JAY A.</creatorcontrib><creatorcontrib>FRÜH, KLAUS</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of the New York Academy of Sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MOSES, ASHLEE V.</au><au>JARVIS, MICHAEL A.</au><au>RAGGO, CAMILO</au><au>BELL, YOLANDA C.</au><au>RUHL, REBECCA</au><au>LUUKKONEN, B.G. MATTIAS</au><au>GRIFFITH, DIANA J.</au><au>WAIT, CECILY L.</au><au>DRUKER, BRIAN J.</au><au>HEINRICH, MICHAEL C.</au><au>NELSON, JAY A.</au><au>FRÜH, KLAUS</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Functional Genomics Approach to Kaposi's Sarcoma</atitle><jtitle>Annals of the New York Academy of Sciences</jtitle><addtitle>Ann N Y Acad Sci</addtitle><date>2002-12</date><risdate>2002</risdate><volume>975</volume><issue>1</issue><spage>180</spage><epage>191</epage><pages>180-191</pages><issn>0077-8923</issn><eissn>1749-6632</eissn><abstract>: Kaposi's sarcoma (KS) is the most frequent malignancy afflicting acquired immune‐deficiency syndrome (AIDS) patients. Tumor lesions are characterized by spindle cells of vascular origin and vascularization. Kaposi's sarcoma‐associated herpes virus (KSHV) is consistently found in all forms of KS. Infection of dermal microvascular endothelial cells (DMVEC) with KSHV recapitulates spindle cell formation in vitro. We studied this transformation process by DNA microarray analysis comparing the RNA expression profiles of KSHV‐infected and mock‐infected DMVEC. Genes involved in tumorigenesis, angiogenesis, host defense, cell growth and differentiation, transcription, and metabolism were observed to change significantly upon infection with KSHV. One of the most consistently KSHV‐induced genes was the receptor tyrosine kinase and proto‐oncogene c‐Kit. Inhibition of c‐Kit activity with the pharmacological inhibitor of c‐Kit signaling STI571 reversed the KSHV‐induced morphological transformation of DMVEC. Moreover, overexpression studies showed that c‐Kit was sufficient to induce spindle cell formation (Moses et al. J. Virol. 76(16): 8383‐8399). These data demonstrate that microarrays are useful for the identification of pharmacological targets essential for KS tumorigenesis.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>12538164</pmid><doi>10.1111/j.1749-6632.2002.tb05951.x</doi><tpages>12</tpages></addata></record> |
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| subjects | antisense Benzamides c-kit Cell Line, Transformed Cell Transformation, Neoplastic - drug effects Cell Transformation, Neoplastic - genetics Cell Transformation, Viral - drug effects Cell Transformation, Viral - genetics Endothelium, Vascular - drug effects Endothelium, Vascular - pathology Endothelium, Vascular - virology Enzyme Inhibitors - pharmacology Gene Expression Profiling Genomics Herpesvirus 8, Human - genetics Herpesvirus 8, Human - pathogenicity Humans Imatinib Mesylate Kaposi's sarcoma-associated herpesvirus microarray Oligonucleotide Array Sequence Analysis Piperazines - pharmacology Proto-Oncogene Proteins c-kit - genetics Pyrimidines - pharmacology RNA, Antisense - genetics RNA, Antisense - pharmacology Sarcoma, Kaposi - etiology Sarcoma, Kaposi - genetics Virulence - genetics |
| title | A Functional Genomics Approach to Kaposi's Sarcoma |
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