The Granulin-Epithelin Precursor/PC-Cell-derived Growth Factor Is a Growth Factor for Epithelial Ovarian Cancer
Purpose: The role of growth factors in ovarian cancer development and progression is complex and multifactorial. We hypothesized that new growth factors may be identified through the molecular analysis of ovarian tumors as they exist in their native environment. Experimental Design: RNA extracted fr...
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| Veröffentlicht in: | Clinical cancer research 2003-01, Vol.9 (1), p.44-51 |
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| creator | JONES, Monica Brown MICHENER, Chad M KOHN, Elise C BLANCHETTE, James O KUZNETSOV, Vladimir A RAFFELD, Mark SERRERO, Ginette EMMERT-BUCK, Michael R PETRICOIN, Emanuel F KRIZMAN, David B LIOTTA, Lance A |
| description | Purpose: The role of growth factors in ovarian cancer development and progression is complex and multifactorial. We hypothesized that
new growth factors may be identified through the molecular analysis of ovarian tumors as they exist in their native environment.
Experimental Design: RNA extracted from microdissected serous low malignant potential (LMP) and invasive ovarian tumors was used to construct
cDNA libraries. A total of 7300 transcripts were randomly chosen for sequencing, and those transcripts were statistically
evaluated. Reverse transcription-PCR and immunohistochemistry were used to validate the findings in tumor tissue samples.
Ovarian cancer cell lines were used to test gene effects on monolayer growth, proliferative capacity, and density-independent
growth.
Results: Analysis of the pooled library transcripts revealed 26 genes differentially expressed between LMP and invasive ovarian cancers.
The granulin-epithelin precursor [GEP/PC-cell derived growth factor (PCDGF)] was expressed only in the invasive ovarian cancer
libraries ( P < 0.028) and was absent in the LMP libraries (0 of 2872 clones). All of the invasive tumor epithelia, 20% of the LMP tumor
epithelia, and all of the stroma from both subsets expressed GEP by reverse transcription-PCR. Immunohistochemical staining
for GEP was diffuse and cytosolic in invasive ovarian cancer tumor cells compared with occasional, punctate, and apical staining
in LMP tumor epithelia. Antisense transfection of GEP into ovarian cancer cell lines resulted in down-regulation of GEP production,
reduction in cell growth ( P < 0.002), decrease in the S-phase fraction ( P < 0.04), and loss of density-independent growth potential ( P < 0.01).
Conclusion: cDNA library preparation from microdissected tumor epithelium provided a selective advantage for the identification of growth
factors for epithelial ovarian cancer. Differential granulin expression in tumor samples and the antiproliferative effects
of its antisense down-regulation suggest that GEP may be a new autocrine growth factor and molecular target for epithelial
ovarian cancer. |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_72973113</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>72973113</sourcerecordid><originalsourceid>FETCH-LOGICAL-h269t-a2cff53fb317e73240c81712488af01ee09c628a6ab8cfe019f80b0a51855d273</originalsourceid><addsrcrecordid>eNpdkE9Lw0AUxIMotla_guSit-D-TTZHCW0tFNpDPYeX7VuzkiZ1N2nx27toS8HD4w3Dj4GZq2hMpcwSzlJ5HTTJVEIEZ6PozvtPQqigRNxGI8okV0KScdRtaoznDtqhsW0y3du-xqDitUM9ON-5l3WRFNg0yRadPeA2wN2xr-MZ6L5z8cLH8M8y4c5B0MSrAzgLbVxAq9HdRzcGGo8Ppz-J3mfTTfGWLFfzRfG6TGqW5n0CTBsjuak4zTDjTBCtaEaZUAoMoYgk1ylTkEKltEFCc6NIRUBSJeWWZXwSPf_l7l33NaDvy531OvSAFrvBlxnLM04pD-DjCRyqHW7LvbM7cN_leaIAPJ0A8BoaE7bS1l84IUJWml642n7UR-uw1L-NHXoEp-syL2kpBP8BQMJ9aQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>72973113</pqid></control><display><type>article</type><title>The Granulin-Epithelin Precursor/PC-Cell-derived Growth Factor Is a Growth Factor for Epithelial Ovarian Cancer</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>JONES, Monica Brown ; MICHENER, Chad M ; KOHN, Elise C ; BLANCHETTE, James O ; KUZNETSOV, Vladimir A ; RAFFELD, Mark ; SERRERO, Ginette ; EMMERT-BUCK, Michael R ; PETRICOIN, Emanuel F ; KRIZMAN, David B ; LIOTTA, Lance A</creator><creatorcontrib>JONES, Monica Brown ; MICHENER, Chad M ; KOHN, Elise C ; BLANCHETTE, James O ; KUZNETSOV, Vladimir A ; RAFFELD, Mark ; SERRERO, Ginette ; EMMERT-BUCK, Michael R ; PETRICOIN, Emanuel F ; KRIZMAN, David B ; LIOTTA, Lance A</creatorcontrib><description>Purpose: The role of growth factors in ovarian cancer development and progression is complex and multifactorial. We hypothesized that
new growth factors may be identified through the molecular analysis of ovarian tumors as they exist in their native environment.
Experimental Design: RNA extracted from microdissected serous low malignant potential (LMP) and invasive ovarian tumors was used to construct
cDNA libraries. A total of 7300 transcripts were randomly chosen for sequencing, and those transcripts were statistically
evaluated. Reverse transcription-PCR and immunohistochemistry were used to validate the findings in tumor tissue samples.
Ovarian cancer cell lines were used to test gene effects on monolayer growth, proliferative capacity, and density-independent
growth.
Results: Analysis of the pooled library transcripts revealed 26 genes differentially expressed between LMP and invasive ovarian cancers.
The granulin-epithelin precursor [GEP/PC-cell derived growth factor (PCDGF)] was expressed only in the invasive ovarian cancer
libraries ( P < 0.028) and was absent in the LMP libraries (0 of 2872 clones). All of the invasive tumor epithelia, 20% of the LMP tumor
epithelia, and all of the stroma from both subsets expressed GEP by reverse transcription-PCR. Immunohistochemical staining
for GEP was diffuse and cytosolic in invasive ovarian cancer tumor cells compared with occasional, punctate, and apical staining
in LMP tumor epithelia. Antisense transfection of GEP into ovarian cancer cell lines resulted in down-regulation of GEP production,
reduction in cell growth ( P < 0.002), decrease in the S-phase fraction ( P < 0.04), and loss of density-independent growth potential ( P < 0.01).
Conclusion: cDNA library preparation from microdissected tumor epithelium provided a selective advantage for the identification of growth
factors for epithelial ovarian cancer. Differential granulin expression in tumor samples and the antiproliferative effects
of its antisense down-regulation suggest that GEP may be a new autocrine growth factor and molecular target for epithelial
ovarian cancer.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 12538450</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Biological and medical sciences ; Cell Division ; Cloning, Molecular ; Databases as Topic ; DNA, Complementary - metabolism ; Epithelium - pathology ; Female ; Female genital diseases ; Gene Library ; Glycoproteins - biosynthesis ; Glycoproteins - genetics ; Growth Substances - biosynthesis ; Growth Substances - genetics ; Growth Substances - metabolism ; Gynecology. Andrology. Obstetrics ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; Medical sciences ; Multigene Family ; Oligonucleotides, Antisense - metabolism ; Ovarian Neoplasms - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Tissue Distribution ; Transfection ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Clinical cancer research, 2003-01, Vol.9 (1), p.44-51</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14472966$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12538450$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>JONES, Monica Brown</creatorcontrib><creatorcontrib>MICHENER, Chad M</creatorcontrib><creatorcontrib>KOHN, Elise C</creatorcontrib><creatorcontrib>BLANCHETTE, James O</creatorcontrib><creatorcontrib>KUZNETSOV, Vladimir A</creatorcontrib><creatorcontrib>RAFFELD, Mark</creatorcontrib><creatorcontrib>SERRERO, Ginette</creatorcontrib><creatorcontrib>EMMERT-BUCK, Michael R</creatorcontrib><creatorcontrib>PETRICOIN, Emanuel F</creatorcontrib><creatorcontrib>KRIZMAN, David B</creatorcontrib><creatorcontrib>LIOTTA, Lance A</creatorcontrib><title>The Granulin-Epithelin Precursor/PC-Cell-derived Growth Factor Is a Growth Factor for Epithelial Ovarian Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: The role of growth factors in ovarian cancer development and progression is complex and multifactorial. We hypothesized that
new growth factors may be identified through the molecular analysis of ovarian tumors as they exist in their native environment.
Experimental Design: RNA extracted from microdissected serous low malignant potential (LMP) and invasive ovarian tumors was used to construct
cDNA libraries. A total of 7300 transcripts were randomly chosen for sequencing, and those transcripts were statistically
evaluated. Reverse transcription-PCR and immunohistochemistry were used to validate the findings in tumor tissue samples.
Ovarian cancer cell lines were used to test gene effects on monolayer growth, proliferative capacity, and density-independent
growth.
Results: Analysis of the pooled library transcripts revealed 26 genes differentially expressed between LMP and invasive ovarian cancers.
The granulin-epithelin precursor [GEP/PC-cell derived growth factor (PCDGF)] was expressed only in the invasive ovarian cancer
libraries ( P < 0.028) and was absent in the LMP libraries (0 of 2872 clones). All of the invasive tumor epithelia, 20% of the LMP tumor
epithelia, and all of the stroma from both subsets expressed GEP by reverse transcription-PCR. Immunohistochemical staining
for GEP was diffuse and cytosolic in invasive ovarian cancer tumor cells compared with occasional, punctate, and apical staining
in LMP tumor epithelia. Antisense transfection of GEP into ovarian cancer cell lines resulted in down-regulation of GEP production,
reduction in cell growth ( P < 0.002), decrease in the S-phase fraction ( P < 0.04), and loss of density-independent growth potential ( P < 0.01).
Conclusion: cDNA library preparation from microdissected tumor epithelium provided a selective advantage for the identification of growth
factors for epithelial ovarian cancer. Differential granulin expression in tumor samples and the antiproliferative effects
of its antisense down-regulation suggest that GEP may be a new autocrine growth factor and molecular target for epithelial
ovarian cancer.</description><subject>Biological and medical sciences</subject><subject>Cell Division</subject><subject>Cloning, Molecular</subject><subject>Databases as Topic</subject><subject>DNA, Complementary - metabolism</subject><subject>Epithelium - pathology</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Gene Library</subject><subject>Glycoproteins - biosynthesis</subject><subject>Glycoproteins - genetics</subject><subject>Growth Substances - biosynthesis</subject><subject>Growth Substances - genetics</subject><subject>Growth Substances - metabolism</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intercellular Signaling Peptides and Proteins</subject><subject>Medical sciences</subject><subject>Multigene Family</subject><subject>Oligonucleotides, Antisense - metabolism</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Time Factors</subject><subject>Tissue Distribution</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE9Lw0AUxIMotla_guSit-D-TTZHCW0tFNpDPYeX7VuzkiZ1N2nx27toS8HD4w3Dj4GZq2hMpcwSzlJ5HTTJVEIEZ6PozvtPQqigRNxGI8okV0KScdRtaoznDtqhsW0y3du-xqDitUM9ON-5l3WRFNg0yRadPeA2wN2xr-MZ6L5z8cLH8M8y4c5B0MSrAzgLbVxAq9HdRzcGGo8Ppz-J3mfTTfGWLFfzRfG6TGqW5n0CTBsjuak4zTDjTBCtaEaZUAoMoYgk1ylTkEKltEFCc6NIRUBSJeWWZXwSPf_l7l33NaDvy531OvSAFrvBlxnLM04pD-DjCRyqHW7LvbM7cN_leaIAPJ0A8BoaE7bS1l84IUJWml642n7UR-uw1L-NHXoEp-syL2kpBP8BQMJ9aQ</recordid><startdate>20030101</startdate><enddate>20030101</enddate><creator>JONES, Monica Brown</creator><creator>MICHENER, Chad M</creator><creator>KOHN, Elise C</creator><creator>BLANCHETTE, James O</creator><creator>KUZNETSOV, Vladimir A</creator><creator>RAFFELD, Mark</creator><creator>SERRERO, Ginette</creator><creator>EMMERT-BUCK, Michael R</creator><creator>PETRICOIN, Emanuel F</creator><creator>KRIZMAN, David B</creator><creator>LIOTTA, Lance A</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20030101</creationdate><title>The Granulin-Epithelin Precursor/PC-Cell-derived Growth Factor Is a Growth Factor for Epithelial Ovarian Cancer</title><author>JONES, Monica Brown ; MICHENER, Chad M ; KOHN, Elise C ; BLANCHETTE, James O ; KUZNETSOV, Vladimir A ; RAFFELD, Mark ; SERRERO, Ginette ; EMMERT-BUCK, Michael R ; PETRICOIN, Emanuel F ; KRIZMAN, David B ; LIOTTA, Lance A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h269t-a2cff53fb317e73240c81712488af01ee09c628a6ab8cfe019f80b0a51855d273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Biological and medical sciences</topic><topic>Cell Division</topic><topic>Cloning, Molecular</topic><topic>Databases as Topic</topic><topic>DNA, Complementary - metabolism</topic><topic>Epithelium - pathology</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Gene Library</topic><topic>Glycoproteins - biosynthesis</topic><topic>Glycoproteins - genetics</topic><topic>Growth Substances - biosynthesis</topic><topic>Growth Substances - genetics</topic><topic>Growth Substances - metabolism</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Intercellular Signaling Peptides and Proteins</topic><topic>Medical sciences</topic><topic>Multigene Family</topic><topic>Oligonucleotides, Antisense - metabolism</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Time Factors</topic><topic>Tissue Distribution</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JONES, Monica Brown</creatorcontrib><creatorcontrib>MICHENER, Chad M</creatorcontrib><creatorcontrib>KOHN, Elise C</creatorcontrib><creatorcontrib>BLANCHETTE, James O</creatorcontrib><creatorcontrib>KUZNETSOV, Vladimir A</creatorcontrib><creatorcontrib>RAFFELD, Mark</creatorcontrib><creatorcontrib>SERRERO, Ginette</creatorcontrib><creatorcontrib>EMMERT-BUCK, Michael R</creatorcontrib><creatorcontrib>PETRICOIN, Emanuel F</creatorcontrib><creatorcontrib>KRIZMAN, David B</creatorcontrib><creatorcontrib>LIOTTA, Lance A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JONES, Monica Brown</au><au>MICHENER, Chad M</au><au>KOHN, Elise C</au><au>BLANCHETTE, James O</au><au>KUZNETSOV, Vladimir A</au><au>RAFFELD, Mark</au><au>SERRERO, Ginette</au><au>EMMERT-BUCK, Michael R</au><au>PETRICOIN, Emanuel F</au><au>KRIZMAN, David B</au><au>LIOTTA, Lance A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Granulin-Epithelin Precursor/PC-Cell-derived Growth Factor Is a Growth Factor for Epithelial Ovarian Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2003-01-01</date><risdate>2003</risdate><volume>9</volume><issue>1</issue><spage>44</spage><epage>51</epage><pages>44-51</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: The role of growth factors in ovarian cancer development and progression is complex and multifactorial. We hypothesized that
new growth factors may be identified through the molecular analysis of ovarian tumors as they exist in their native environment.
Experimental Design: RNA extracted from microdissected serous low malignant potential (LMP) and invasive ovarian tumors was used to construct
cDNA libraries. A total of 7300 transcripts were randomly chosen for sequencing, and those transcripts were statistically
evaluated. Reverse transcription-PCR and immunohistochemistry were used to validate the findings in tumor tissue samples.
Ovarian cancer cell lines were used to test gene effects on monolayer growth, proliferative capacity, and density-independent
growth.
Results: Analysis of the pooled library transcripts revealed 26 genes differentially expressed between LMP and invasive ovarian cancers.
The granulin-epithelin precursor [GEP/PC-cell derived growth factor (PCDGF)] was expressed only in the invasive ovarian cancer
libraries ( P < 0.028) and was absent in the LMP libraries (0 of 2872 clones). All of the invasive tumor epithelia, 20% of the LMP tumor
epithelia, and all of the stroma from both subsets expressed GEP by reverse transcription-PCR. Immunohistochemical staining
for GEP was diffuse and cytosolic in invasive ovarian cancer tumor cells compared with occasional, punctate, and apical staining
in LMP tumor epithelia. Antisense transfection of GEP into ovarian cancer cell lines resulted in down-regulation of GEP production,
reduction in cell growth ( P < 0.002), decrease in the S-phase fraction ( P < 0.04), and loss of density-independent growth potential ( P < 0.01).
Conclusion: cDNA library preparation from microdissected tumor epithelium provided a selective advantage for the identification of growth
factors for epithelial ovarian cancer. Differential granulin expression in tumor samples and the antiproliferative effects
of its antisense down-regulation suggest that GEP may be a new autocrine growth factor and molecular target for epithelial
ovarian cancer.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>12538450</pmid><tpages>8</tpages></addata></record> |
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| subjects | Biological and medical sciences Cell Division Cloning, Molecular Databases as Topic DNA, Complementary - metabolism Epithelium - pathology Female Female genital diseases Gene Library Glycoproteins - biosynthesis Glycoproteins - genetics Growth Substances - biosynthesis Growth Substances - genetics Growth Substances - metabolism Gynecology. Andrology. Obstetrics Humans Immunohistochemistry Intercellular Signaling Peptides and Proteins Medical sciences Multigene Family Oligonucleotides, Antisense - metabolism Ovarian Neoplasms - metabolism Reverse Transcriptase Polymerase Chain Reaction Time Factors Tissue Distribution Transfection Tumor Cells, Cultured Tumors |
| title | The Granulin-Epithelin Precursor/PC-Cell-derived Growth Factor Is a Growth Factor for Epithelial Ovarian Cancer |
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