Monoclonal antibodies recognizing the non-tandem repeat regions of the human mucin MUC4 in pancreatic cancer
The MUC4 mucin is a high molecular weight, membrane-bound, and highly glycosylated protein. It is a multi-domain protein that is putatively cleaved into a large mucin-like subunit (MUC4α) and a C-terminal growth-factor like subunit (MUC4β). MUC4 plays critical roles in physiological and pathological...
Gespeichert in:
| Veröffentlicht in: | PloS one 2011-08, Vol.6 (8), p.e23344-e23344 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e23344 |
|---|---|
| container_issue | 8 |
| container_start_page | e23344 |
| container_title | PloS one |
| container_volume | 6 |
| creator | Jain, Maneesh Venkatraman, Ganesh Moniaux, Nicolas Kaur, Sukhwinder Kumar, Sushil Chakraborty, Subhankar Varshney, Grish C Batra, Surinder K |
| description | The MUC4 mucin is a high molecular weight, membrane-bound, and highly glycosylated protein. It is a multi-domain protein that is putatively cleaved into a large mucin-like subunit (MUC4α) and a C-terminal growth-factor like subunit (MUC4β). MUC4 plays critical roles in physiological and pathological conditions and is aberrantly overexpressed in several cancers, including those of the pancreas, cervix, breast and lung. It is also a potential biomarker for the diagnosis, prognosis and progression of several malignancies. Further, MUC4 plays diverse functional roles in cancer initiation and progression as evident from its involvement in oncogenic transformation, proliferation, inhibition of apoptosis, motility and invasion, and resistance to chemotherapy in human cancer cells. We have previously generated a monoclonal antibody 8G7, which is directed against the TR region of MUC4, and has been extensively used to study the expression of MUC4 in several malignancies. Here, we describe the generation of anti-MUC4 antibodies directed against the non-TR regions of MUC4. Recombinant glutathione-S-transferase (GST)-fused MUC4α fragments, both upstream (MUC4α-N-Ter) and downstream (MUC4α-C-Ter) of the TR domain, were used as immunogens to immunize BALB/c mice. Following cell fusion, hybridomas were screened using the aforementioned recombinant proteins ad lysates from human pancreatic cell lines. Three anti MUC4α-N-Ter and one anti-MUC4α-C-Ter antibodies were characterized by several inmmunoassays including enzyme-linked immunosorbent assay (ELISA), immunoblotting, immunofluorescene, flow cytometry and immunoprecipitation using MUC4 expressing human pancreatic cancer cell lines. The antibodies also reacted with the MUC4 in human pancreatic tumor sections in immunohistochemical analysis. The new domain-specific anti-MUC4 antibodies will serve as important reagents to study the structure-function relationship of MUC4 domains and for the development of MUC4-based diagnostics and therapeutics. |
| doi_str_mv | 10.1371/journal.pone.0023344 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1308334805</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A476881848</galeid><doaj_id>oai_doaj_org_article_705978b5c72246d08efcc2b87c3d2a3b</doaj_id><sourcerecordid>A476881848</sourcerecordid><originalsourceid>FETCH-LOGICAL-c691t-138eabb762a3ec48cd81629effdd9e8435fe440168487b32646ac7780ebb9bc83</originalsourceid><addsrcrecordid>eNqNk9Fu0zAUhiMEYqPwBggiIYF20WLHru3cIE0VsEqbJgHj1nKck9SVYxc7QcDT467Z1KBdIF8cy_7O7-PfPln2EqMFJhy_3_ohOGUXO-9ggVBBCKWPslNckmLOCkQeH81PsmcxbhFaEsHY0-ykwEIwLthpZq-889r6pJQr15vK1wZiHkD71pk_xrV5v4HceTfvlauhS1s7UH0KrfEu5r65BTZDp1zeDdq4_OpmRfMUd8rpkFijc52mEJ5nTxplI7wY4yy7-fTx2-pifnn9eb06v5xrVuJ-jokAVVWcFYqApkLXArOihKap6xIEJcsGKEWYCSp4RQpGmdKcCwRVVVZakFn2-qC7sz7K0agoMUEiuSSSDbNsfSBqr7ZyF0ynwm_plZG3Cz60UoVUuAXJ0bLkolpqXhSU1UhAo3VRCa5JnQqsktaH8bSh6qDW4Pqg7ER0uuPMRrb-pySYIYJQEng3CgT_Y4DYy85EDdYqB36IUgi-RAXl-7Lf_EM-fLmRalWq37jGp2P1XlOeU86EwMm4RC0eoNJIj2x0-lSNSeuThLNJQmJ6-NW3aohRrr9--X_2-vuUfXvEbkDZfhO9Hfr9_5qC9ADq4GMM0Nx7jJHc98SdG3LfE3LsiZT26vh97pPumoD8BUdpB2k</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1308334805</pqid></control><display><type>article</type><title>Monoclonal antibodies recognizing the non-tandem repeat regions of the human mucin MUC4 in pancreatic cancer</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Jain, Maneesh ; Venkatraman, Ganesh ; Moniaux, Nicolas ; Kaur, Sukhwinder ; Kumar, Sushil ; Chakraborty, Subhankar ; Varshney, Grish C ; Batra, Surinder K</creator><creatorcontrib>Jain, Maneesh ; Venkatraman, Ganesh ; Moniaux, Nicolas ; Kaur, Sukhwinder ; Kumar, Sushil ; Chakraborty, Subhankar ; Varshney, Grish C ; Batra, Surinder K</creatorcontrib><description>The MUC4 mucin is a high molecular weight, membrane-bound, and highly glycosylated protein. It is a multi-domain protein that is putatively cleaved into a large mucin-like subunit (MUC4α) and a C-terminal growth-factor like subunit (MUC4β). MUC4 plays critical roles in physiological and pathological conditions and is aberrantly overexpressed in several cancers, including those of the pancreas, cervix, breast and lung. It is also a potential biomarker for the diagnosis, prognosis and progression of several malignancies. Further, MUC4 plays diverse functional roles in cancer initiation and progression as evident from its involvement in oncogenic transformation, proliferation, inhibition of apoptosis, motility and invasion, and resistance to chemotherapy in human cancer cells. We have previously generated a monoclonal antibody 8G7, which is directed against the TR region of MUC4, and has been extensively used to study the expression of MUC4 in several malignancies. Here, we describe the generation of anti-MUC4 antibodies directed against the non-TR regions of MUC4. Recombinant glutathione-S-transferase (GST)-fused MUC4α fragments, both upstream (MUC4α-N-Ter) and downstream (MUC4α-C-Ter) of the TR domain, were used as immunogens to immunize BALB/c mice. Following cell fusion, hybridomas were screened using the aforementioned recombinant proteins ad lysates from human pancreatic cell lines. Three anti MUC4α-N-Ter and one anti-MUC4α-C-Ter antibodies were characterized by several inmmunoassays including enzyme-linked immunosorbent assay (ELISA), immunoblotting, immunofluorescene, flow cytometry and immunoprecipitation using MUC4 expressing human pancreatic cancer cell lines. The antibodies also reacted with the MUC4 in human pancreatic tumor sections in immunohistochemical analysis. The new domain-specific anti-MUC4 antibodies will serve as important reagents to study the structure-function relationship of MUC4 domains and for the development of MUC4-based diagnostics and therapeutics.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0023344</identifier><identifier>PMID: 21886786</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animals ; Antibodies, Monoclonal - immunology ; Apoptosis ; Biochemistry ; Biology ; Biomarkers ; Biotechnology ; Cancer ; Cell fusion ; Cell Line, Tumor ; Cell Membrane - metabolism ; Cervix ; Chemotherapy ; Cloning ; Cytometry ; Development and progression ; Diagnosis ; Enzyme-linked immunosorbent assay ; Flow cytometry ; Fluorescent Antibody Technique ; Glutathione ; Glutathione transferase ; Growth factors ; Humans ; Immunization ; Immunoblotting ; Immunoglobulins ; Immunoprecipitation ; Laboratories ; Lung cancer ; Lysates ; Medicine ; Mice ; Molecular biology ; Molecular weight ; Monoclonal antibodies ; Motility ; Mucin ; Mucin-4 - chemistry ; Mucin-4 - immunology ; Mucins ; Ovarian cancer ; Pancreas ; Pancreatic cancer ; Pancreatic Neoplasms - immunology ; Peroxidase - metabolism ; Physiological aspects ; Physiological effects ; Protein Binding ; Proteins ; Reagents ; Recombinant proteins ; Recombinant Proteins - chemistry ; Recombinant Proteins - immunology ; Structure-function relationships ; Studies ; Tandem Repeat Sequences - immunology ; Transformation ; Tumor cell lines</subject><ispartof>PloS one, 2011-08, Vol.6 (8), p.e23344-e23344</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Jain et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Jain et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-138eabb762a3ec48cd81629effdd9e8435fe440168487b32646ac7780ebb9bc83</citedby><cites>FETCH-LOGICAL-c691t-138eabb762a3ec48cd81629effdd9e8435fe440168487b32646ac7780ebb9bc83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160300/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160300/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21886786$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jain, Maneesh</creatorcontrib><creatorcontrib>Venkatraman, Ganesh</creatorcontrib><creatorcontrib>Moniaux, Nicolas</creatorcontrib><creatorcontrib>Kaur, Sukhwinder</creatorcontrib><creatorcontrib>Kumar, Sushil</creatorcontrib><creatorcontrib>Chakraborty, Subhankar</creatorcontrib><creatorcontrib>Varshney, Grish C</creatorcontrib><creatorcontrib>Batra, Surinder K</creatorcontrib><title>Monoclonal antibodies recognizing the non-tandem repeat regions of the human mucin MUC4 in pancreatic cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The MUC4 mucin is a high molecular weight, membrane-bound, and highly glycosylated protein. It is a multi-domain protein that is putatively cleaved into a large mucin-like subunit (MUC4α) and a C-terminal growth-factor like subunit (MUC4β). MUC4 plays critical roles in physiological and pathological conditions and is aberrantly overexpressed in several cancers, including those of the pancreas, cervix, breast and lung. It is also a potential biomarker for the diagnosis, prognosis and progression of several malignancies. Further, MUC4 plays diverse functional roles in cancer initiation and progression as evident from its involvement in oncogenic transformation, proliferation, inhibition of apoptosis, motility and invasion, and resistance to chemotherapy in human cancer cells. We have previously generated a monoclonal antibody 8G7, which is directed against the TR region of MUC4, and has been extensively used to study the expression of MUC4 in several malignancies. Here, we describe the generation of anti-MUC4 antibodies directed against the non-TR regions of MUC4. Recombinant glutathione-S-transferase (GST)-fused MUC4α fragments, both upstream (MUC4α-N-Ter) and downstream (MUC4α-C-Ter) of the TR domain, were used as immunogens to immunize BALB/c mice. Following cell fusion, hybridomas were screened using the aforementioned recombinant proteins ad lysates from human pancreatic cell lines. Three anti MUC4α-N-Ter and one anti-MUC4α-C-Ter antibodies were characterized by several inmmunoassays including enzyme-linked immunosorbent assay (ELISA), immunoblotting, immunofluorescene, flow cytometry and immunoprecipitation using MUC4 expressing human pancreatic cancer cell lines. The antibodies also reacted with the MUC4 in human pancreatic tumor sections in immunohistochemical analysis. The new domain-specific anti-MUC4 antibodies will serve as important reagents to study the structure-function relationship of MUC4 domains and for the development of MUC4-based diagnostics and therapeutics.</description><subject>Analysis</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cell fusion</subject><subject>Cell Line, Tumor</subject><subject>Cell Membrane - metabolism</subject><subject>Cervix</subject><subject>Chemotherapy</subject><subject>Cloning</subject><subject>Cytometry</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Flow cytometry</subject><subject>Fluorescent Antibody Technique</subject><subject>Glutathione</subject><subject>Glutathione transferase</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunoblotting</subject><subject>Immunoglobulins</subject><subject>Immunoprecipitation</subject><subject>Laboratories</subject><subject>Lung cancer</subject><subject>Lysates</subject><subject>Medicine</subject><subject>Mice</subject><subject>Molecular biology</subject><subject>Molecular weight</subject><subject>Monoclonal antibodies</subject><subject>Motility</subject><subject>Mucin</subject><subject>Mucin-4 - chemistry</subject><subject>Mucin-4 - immunology</subject><subject>Mucins</subject><subject>Ovarian cancer</subject><subject>Pancreas</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - immunology</subject><subject>Peroxidase - metabolism</subject><subject>Physiological aspects</subject><subject>Physiological effects</subject><subject>Protein Binding</subject><subject>Proteins</subject><subject>Reagents</subject><subject>Recombinant proteins</subject><subject>Recombinant Proteins - chemistry</subject><subject>Recombinant Proteins - immunology</subject><subject>Structure-function relationships</subject><subject>Studies</subject><subject>Tandem Repeat Sequences - immunology</subject><subject>Transformation</subject><subject>Tumor cell lines</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9Fu0zAUhiMEYqPwBggiIYF20WLHru3cIE0VsEqbJgHj1nKck9SVYxc7QcDT467Z1KBdIF8cy_7O7-PfPln2EqMFJhy_3_ohOGUXO-9ggVBBCKWPslNckmLOCkQeH81PsmcxbhFaEsHY0-ykwEIwLthpZq-889r6pJQr15vK1wZiHkD71pk_xrV5v4HceTfvlauhS1s7UH0KrfEu5r65BTZDp1zeDdq4_OpmRfMUd8rpkFijc52mEJ5nTxplI7wY4yy7-fTx2-pifnn9eb06v5xrVuJ-jokAVVWcFYqApkLXArOihKap6xIEJcsGKEWYCSp4RQpGmdKcCwRVVVZakFn2-qC7sz7K0agoMUEiuSSSDbNsfSBqr7ZyF0ynwm_plZG3Cz60UoVUuAXJ0bLkolpqXhSU1UhAo3VRCa5JnQqsktaH8bSh6qDW4Pqg7ER0uuPMRrb-pySYIYJQEng3CgT_Y4DYy85EDdYqB36IUgi-RAXl-7Lf_EM-fLmRalWq37jGp2P1XlOeU86EwMm4RC0eoNJIj2x0-lSNSeuThLNJQmJ6-NW3aohRrr9--X_2-vuUfXvEbkDZfhO9Hfr9_5qC9ADq4GMM0Nx7jJHc98SdG3LfE3LsiZT26vh97pPumoD8BUdpB2k</recordid><startdate>20110823</startdate><enddate>20110823</enddate><creator>Jain, Maneesh</creator><creator>Venkatraman, Ganesh</creator><creator>Moniaux, Nicolas</creator><creator>Kaur, Sukhwinder</creator><creator>Kumar, Sushil</creator><creator>Chakraborty, Subhankar</creator><creator>Varshney, Grish C</creator><creator>Batra, Surinder K</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110823</creationdate><title>Monoclonal antibodies recognizing the non-tandem repeat regions of the human mucin MUC4 in pancreatic cancer</title><author>Jain, Maneesh ; Venkatraman, Ganesh ; Moniaux, Nicolas ; Kaur, Sukhwinder ; Kumar, Sushil ; Chakraborty, Subhankar ; Varshney, Grish C ; Batra, Surinder K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-138eabb762a3ec48cd81629effdd9e8435fe440168487b32646ac7780ebb9bc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Cell fusion</topic><topic>Cell Line, Tumor</topic><topic>Cell Membrane - metabolism</topic><topic>Cervix</topic><topic>Chemotherapy</topic><topic>Cloning</topic><topic>Cytometry</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Flow cytometry</topic><topic>Fluorescent Antibody Technique</topic><topic>Glutathione</topic><topic>Glutathione transferase</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Immunization</topic><topic>Immunoblotting</topic><topic>Immunoglobulins</topic><topic>Immunoprecipitation</topic><topic>Laboratories</topic><topic>Lung cancer</topic><topic>Lysates</topic><topic>Medicine</topic><topic>Mice</topic><topic>Molecular biology</topic><topic>Molecular weight</topic><topic>Monoclonal antibodies</topic><topic>Motility</topic><topic>Mucin</topic><topic>Mucin-4 - chemistry</topic><topic>Mucin-4 - immunology</topic><topic>Mucins</topic><topic>Ovarian cancer</topic><topic>Pancreas</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - immunology</topic><topic>Peroxidase - metabolism</topic><topic>Physiological aspects</topic><topic>Physiological effects</topic><topic>Protein Binding</topic><topic>Proteins</topic><topic>Reagents</topic><topic>Recombinant proteins</topic><topic>Recombinant Proteins - chemistry</topic><topic>Recombinant Proteins - immunology</topic><topic>Structure-function relationships</topic><topic>Studies</topic><topic>Tandem Repeat Sequences - immunology</topic><topic>Transformation</topic><topic>Tumor cell lines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jain, Maneesh</creatorcontrib><creatorcontrib>Venkatraman, Ganesh</creatorcontrib><creatorcontrib>Moniaux, Nicolas</creatorcontrib><creatorcontrib>Kaur, Sukhwinder</creatorcontrib><creatorcontrib>Kumar, Sushil</creatorcontrib><creatorcontrib>Chakraborty, Subhankar</creatorcontrib><creatorcontrib>Varshney, Grish C</creatorcontrib><creatorcontrib>Batra, Surinder K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jain, Maneesh</au><au>Venkatraman, Ganesh</au><au>Moniaux, Nicolas</au><au>Kaur, Sukhwinder</au><au>Kumar, Sushil</au><au>Chakraborty, Subhankar</au><au>Varshney, Grish C</au><au>Batra, Surinder K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Monoclonal antibodies recognizing the non-tandem repeat regions of the human mucin MUC4 in pancreatic cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-08-23</date><risdate>2011</risdate><volume>6</volume><issue>8</issue><spage>e23344</spage><epage>e23344</epage><pages>e23344-e23344</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The MUC4 mucin is a high molecular weight, membrane-bound, and highly glycosylated protein. It is a multi-domain protein that is putatively cleaved into a large mucin-like subunit (MUC4α) and a C-terminal growth-factor like subunit (MUC4β). MUC4 plays critical roles in physiological and pathological conditions and is aberrantly overexpressed in several cancers, including those of the pancreas, cervix, breast and lung. It is also a potential biomarker for the diagnosis, prognosis and progression of several malignancies. Further, MUC4 plays diverse functional roles in cancer initiation and progression as evident from its involvement in oncogenic transformation, proliferation, inhibition of apoptosis, motility and invasion, and resistance to chemotherapy in human cancer cells. We have previously generated a monoclonal antibody 8G7, which is directed against the TR region of MUC4, and has been extensively used to study the expression of MUC4 in several malignancies. Here, we describe the generation of anti-MUC4 antibodies directed against the non-TR regions of MUC4. Recombinant glutathione-S-transferase (GST)-fused MUC4α fragments, both upstream (MUC4α-N-Ter) and downstream (MUC4α-C-Ter) of the TR domain, were used as immunogens to immunize BALB/c mice. Following cell fusion, hybridomas were screened using the aforementioned recombinant proteins ad lysates from human pancreatic cell lines. Three anti MUC4α-N-Ter and one anti-MUC4α-C-Ter antibodies were characterized by several inmmunoassays including enzyme-linked immunosorbent assay (ELISA), immunoblotting, immunofluorescene, flow cytometry and immunoprecipitation using MUC4 expressing human pancreatic cancer cell lines. The antibodies also reacted with the MUC4 in human pancreatic tumor sections in immunohistochemical analysis. The new domain-specific anti-MUC4 antibodies will serve as important reagents to study the structure-function relationship of MUC4 domains and for the development of MUC4-based diagnostics and therapeutics.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21886786</pmid><doi>10.1371/journal.pone.0023344</doi><tpages>e23344</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-08, Vol.6 (8), p.e23344-e23344 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1308334805 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Analysis Animals Antibodies, Monoclonal - immunology Apoptosis Biochemistry Biology Biomarkers Biotechnology Cancer Cell fusion Cell Line, Tumor Cell Membrane - metabolism Cervix Chemotherapy Cloning Cytometry Development and progression Diagnosis Enzyme-linked immunosorbent assay Flow cytometry Fluorescent Antibody Technique Glutathione Glutathione transferase Growth factors Humans Immunization Immunoblotting Immunoglobulins Immunoprecipitation Laboratories Lung cancer Lysates Medicine Mice Molecular biology Molecular weight Monoclonal antibodies Motility Mucin Mucin-4 - chemistry Mucin-4 - immunology Mucins Ovarian cancer Pancreas Pancreatic cancer Pancreatic Neoplasms - immunology Peroxidase - metabolism Physiological aspects Physiological effects Protein Binding Proteins Reagents Recombinant proteins Recombinant Proteins - chemistry Recombinant Proteins - immunology Structure-function relationships Studies Tandem Repeat Sequences - immunology Transformation Tumor cell lines |
| title | Monoclonal antibodies recognizing the non-tandem repeat regions of the human mucin MUC4 in pancreatic cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T23%3A55%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Monoclonal%20antibodies%20recognizing%20the%20non-tandem%20repeat%20regions%20of%20the%20human%20mucin%20MUC4%20in%20pancreatic%20cancer&rft.jtitle=PloS%20one&rft.au=Jain,%20Maneesh&rft.date=2011-08-23&rft.volume=6&rft.issue=8&rft.spage=e23344&rft.epage=e23344&rft.pages=e23344-e23344&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0023344&rft_dat=%3Cgale_plos_%3EA476881848%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1308334805&rft_id=info:pmid/21886786&rft_galeid=A476881848&rft_doaj_id=oai_doaj_org_article_705978b5c72246d08efcc2b87c3d2a3b&rfr_iscdi=true |