Mucin 1 Regulates Cox-2 Gene in Pancreatic Cancer
Eighty percent of pancreatic ductal adenocarcinomas (PDAs) overexpress mucin 1 (MUC1), a transmembrane mucin glycoprotein. MUC1(high) PDA patients also express high levels of cyclooxygenase 2 (COX-2) and show poor prognosis. The cytoplasmic tail of MUC1 (MUC1-CT) partakes in oncogenic signaling, res...
Gespeichert in:
| Veröffentlicht in: | Pancreas 2015-08, Vol.44 (6), p.909-917 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 917 |
|---|---|
| container_issue | 6 |
| container_start_page | 909 |
| container_title | Pancreas |
| container_volume | 44 |
| creator | Nath, Sritama Roy, Lopamudra Das Grover, Priyanka Rao, Shanti Mukherjee, Pinku |
| description | Eighty percent of pancreatic ductal adenocarcinomas (PDAs) overexpress mucin 1 (MUC1), a transmembrane mucin glycoprotein. MUC1(high) PDA patients also express high levels of cyclooxygenase 2 (COX-2) and show poor prognosis. The cytoplasmic tail of MUC1 (MUC1-CT) partakes in oncogenic signaling, resulting in accelerated cancer progression. Our aim was to understand the regulation of Cox-2 expression by MUC1.
Levels of COX-2 and MUC1 were determined in MUC1(-/-), MUC1(low), and MUC1(high) PDA cells and tumors using reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry. Proliferative and invasive potential was assessed using MTT and Boyden chamber assays. Chromatin immunoprecipitation was performed to evaluate binding of MUC1-CT to the promoter of COX-2 gene.
Significantly higher levels of COX-2 mRNA and protein were detected in MUC1(high) versus MUC1(low/null) cells, which were recapitulated in vivo. In addition, deletion of MUC1 gene and transient knockdown of MUC1 led to decreased COX-2 level. Also, MUC1-CT associated with the COX-2 promoter at ∼1000 base pairs upstream of the transcription start site, the same gene locus where nuclear factor κB p65 associates with the COX-2 promoter.
Data supports a novel regulation of COX-2 gene by MUC1 in PDA, the intervention of which may lead to a better therapeutic targeting in PDA patients. |
| doi_str_mv | 10.1097/MPA.0000000000000371 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4500655</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1696186334</sourcerecordid><originalsourceid>FETCH-LOGICAL-c459t-b7b0783810b8583cdfd1e2d8b873b2fee6585901dffb3104d99234cced2c8e223</originalsourceid><addsrcrecordid>eNpdkNFLwzAQxoMobk7_A5E--tKZS5omfRFGmVPYcIg-hzS9zkrXzqQV_e-tbI7pvdzB9913x4-QS6BjoIm8WSwnY3pYXMIRGYLgcRgppo7JkColQg5SDsiZ92-UguQiOSUDFlMugPEhgUVnyzqA4AlXXWVa9EHafIYsmGGNQa8sTW0dmra0QdqP6M7JSWEqjxe7PiIvd9Pn9D6cP84e0sk8tJFI2jCTGZWKK6CZEorbvMgBWa4yJXnGCsRYKJFQyIsi40CjPEkYj6zFnFmFjPERud3mbrpsjbnFunWm0htXro370o0p9V-lLl_1qvnQkaA0FqIPuN4FuOa9Q9_qdektVpWpsem8hjiJQcWcR7012lqta7x3WOzPANU_tHVPW_-n3a9dHb64X_rFy78BSZJ5NA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1696186334</pqid></control><display><type>article</type><title>Mucin 1 Regulates Cox-2 Gene in Pancreatic Cancer</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><creator>Nath, Sritama ; Roy, Lopamudra Das ; Grover, Priyanka ; Rao, Shanti ; Mukherjee, Pinku</creator><creatorcontrib>Nath, Sritama ; Roy, Lopamudra Das ; Grover, Priyanka ; Rao, Shanti ; Mukherjee, Pinku</creatorcontrib><description>Eighty percent of pancreatic ductal adenocarcinomas (PDAs) overexpress mucin 1 (MUC1), a transmembrane mucin glycoprotein. MUC1(high) PDA patients also express high levels of cyclooxygenase 2 (COX-2) and show poor prognosis. The cytoplasmic tail of MUC1 (MUC1-CT) partakes in oncogenic signaling, resulting in accelerated cancer progression. Our aim was to understand the regulation of Cox-2 expression by MUC1.
Levels of COX-2 and MUC1 were determined in MUC1(-/-), MUC1(low), and MUC1(high) PDA cells and tumors using reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry. Proliferative and invasive potential was assessed using MTT and Boyden chamber assays. Chromatin immunoprecipitation was performed to evaluate binding of MUC1-CT to the promoter of COX-2 gene.
Significantly higher levels of COX-2 mRNA and protein were detected in MUC1(high) versus MUC1(low/null) cells, which were recapitulated in vivo. In addition, deletion of MUC1 gene and transient knockdown of MUC1 led to decreased COX-2 level. Also, MUC1-CT associated with the COX-2 promoter at ∼1000 base pairs upstream of the transcription start site, the same gene locus where nuclear factor κB p65 associates with the COX-2 promoter.
Data supports a novel regulation of COX-2 gene by MUC1 in PDA, the intervention of which may lead to a better therapeutic targeting in PDA patients.</description><identifier>ISSN: 0885-3177</identifier><identifier>EISSN: 1536-4828</identifier><identifier>DOI: 10.1097/MPA.0000000000000371</identifier><identifier>PMID: 26035123</identifier><language>eng</language><publisher>United States: Lippincott Williams & Wilkins</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; Binding Sites ; Carcinoma, Pancreatic Ductal - drug therapy ; Carcinoma, Pancreatic Ductal - enzymology ; Carcinoma, Pancreatic Ductal - genetics ; Carcinoma, Pancreatic Ductal - pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation - drug effects ; Cyclooxygenase 2 - genetics ; Cyclooxygenase 2 - metabolism ; Cyclooxygenase 2 Inhibitors - pharmacology ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Mice, Nude ; Mucin-1 - genetics ; Mucin-1 - metabolism ; Neoplasm Invasiveness ; Original ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - enzymology ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - pathology ; Promoter Regions, Genetic ; RNA Interference ; RNA, Messenger - metabolism ; Transcription Factor RelA - metabolism ; Transfection ; Xenograft Model Antitumor Assays</subject><ispartof>Pancreas, 2015-08, Vol.44 (6), p.909-917</ispartof><rights>Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. 2015 Wolters Kluwer Health, Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-b7b0783810b8583cdfd1e2d8b873b2fee6585901dffb3104d99234cced2c8e223</citedby><cites>FETCH-LOGICAL-c459t-b7b0783810b8583cdfd1e2d8b873b2fee6585901dffb3104d99234cced2c8e223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26035123$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nath, Sritama</creatorcontrib><creatorcontrib>Roy, Lopamudra Das</creatorcontrib><creatorcontrib>Grover, Priyanka</creatorcontrib><creatorcontrib>Rao, Shanti</creatorcontrib><creatorcontrib>Mukherjee, Pinku</creatorcontrib><title>Mucin 1 Regulates Cox-2 Gene in Pancreatic Cancer</title><title>Pancreas</title><addtitle>Pancreas</addtitle><description>Eighty percent of pancreatic ductal adenocarcinomas (PDAs) overexpress mucin 1 (MUC1), a transmembrane mucin glycoprotein. MUC1(high) PDA patients also express high levels of cyclooxygenase 2 (COX-2) and show poor prognosis. The cytoplasmic tail of MUC1 (MUC1-CT) partakes in oncogenic signaling, resulting in accelerated cancer progression. Our aim was to understand the regulation of Cox-2 expression by MUC1.
Levels of COX-2 and MUC1 were determined in MUC1(-/-), MUC1(low), and MUC1(high) PDA cells and tumors using reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry. Proliferative and invasive potential was assessed using MTT and Boyden chamber assays. Chromatin immunoprecipitation was performed to evaluate binding of MUC1-CT to the promoter of COX-2 gene.
Significantly higher levels of COX-2 mRNA and protein were detected in MUC1(high) versus MUC1(low/null) cells, which were recapitulated in vivo. In addition, deletion of MUC1 gene and transient knockdown of MUC1 led to decreased COX-2 level. Also, MUC1-CT associated with the COX-2 promoter at ∼1000 base pairs upstream of the transcription start site, the same gene locus where nuclear factor κB p65 associates with the COX-2 promoter.
Data supports a novel regulation of COX-2 gene by MUC1 in PDA, the intervention of which may lead to a better therapeutic targeting in PDA patients.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Binding Sites</subject><subject>Carcinoma, Pancreatic Ductal - drug therapy</subject><subject>Carcinoma, Pancreatic Ductal - enzymology</subject><subject>Carcinoma, Pancreatic Ductal - genetics</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Proliferation - drug effects</subject><subject>Cyclooxygenase 2 - genetics</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Cyclooxygenase 2 Inhibitors - pharmacology</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Mice, Nude</subject><subject>Mucin-1 - genetics</subject><subject>Mucin-1 - metabolism</subject><subject>Neoplasm Invasiveness</subject><subject>Original</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - enzymology</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Promoter Regions, Genetic</subject><subject>RNA Interference</subject><subject>RNA, Messenger - metabolism</subject><subject>Transcription Factor RelA - metabolism</subject><subject>Transfection</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0885-3177</issn><issn>1536-4828</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkNFLwzAQxoMobk7_A5E--tKZS5omfRFGmVPYcIg-hzS9zkrXzqQV_e-tbI7pvdzB9913x4-QS6BjoIm8WSwnY3pYXMIRGYLgcRgppo7JkColQg5SDsiZ92-UguQiOSUDFlMugPEhgUVnyzqA4AlXXWVa9EHafIYsmGGNQa8sTW0dmra0QdqP6M7JSWEqjxe7PiIvd9Pn9D6cP84e0sk8tJFI2jCTGZWKK6CZEorbvMgBWa4yJXnGCsRYKJFQyIsi40CjPEkYj6zFnFmFjPERud3mbrpsjbnFunWm0htXro370o0p9V-lLl_1qvnQkaA0FqIPuN4FuOa9Q9_qdektVpWpsem8hjiJQcWcR7012lqta7x3WOzPANU_tHVPW_-n3a9dHb64X_rFy78BSZJ5NA</recordid><startdate>20150801</startdate><enddate>20150801</enddate><creator>Nath, Sritama</creator><creator>Roy, Lopamudra Das</creator><creator>Grover, Priyanka</creator><creator>Rao, Shanti</creator><creator>Mukherjee, Pinku</creator><general>Lippincott Williams & Wilkins</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150801</creationdate><title>Mucin 1 Regulates Cox-2 Gene in Pancreatic Cancer</title><author>Nath, Sritama ; Roy, Lopamudra Das ; Grover, Priyanka ; Rao, Shanti ; Mukherjee, Pinku</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-b7b0783810b8583cdfd1e2d8b873b2fee6585901dffb3104d99234cced2c8e223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Binding Sites</topic><topic>Carcinoma, Pancreatic Ductal - drug therapy</topic><topic>Carcinoma, Pancreatic Ductal - enzymology</topic><topic>Carcinoma, Pancreatic Ductal - genetics</topic><topic>Carcinoma, Pancreatic Ductal - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Proliferation - drug effects</topic><topic>Cyclooxygenase 2 - genetics</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Cyclooxygenase 2 Inhibitors - pharmacology</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Mice, Nude</topic><topic>Mucin-1 - genetics</topic><topic>Mucin-1 - metabolism</topic><topic>Neoplasm Invasiveness</topic><topic>Original</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - enzymology</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Promoter Regions, Genetic</topic><topic>RNA Interference</topic><topic>RNA, Messenger - metabolism</topic><topic>Transcription Factor RelA - metabolism</topic><topic>Transfection</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nath, Sritama</creatorcontrib><creatorcontrib>Roy, Lopamudra Das</creatorcontrib><creatorcontrib>Grover, Priyanka</creatorcontrib><creatorcontrib>Rao, Shanti</creatorcontrib><creatorcontrib>Mukherjee, Pinku</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pancreas</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nath, Sritama</au><au>Roy, Lopamudra Das</au><au>Grover, Priyanka</au><au>Rao, Shanti</au><au>Mukherjee, Pinku</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mucin 1 Regulates Cox-2 Gene in Pancreatic Cancer</atitle><jtitle>Pancreas</jtitle><addtitle>Pancreas</addtitle><date>2015-08-01</date><risdate>2015</risdate><volume>44</volume><issue>6</issue><spage>909</spage><epage>917</epage><pages>909-917</pages><issn>0885-3177</issn><eissn>1536-4828</eissn><abstract>Eighty percent of pancreatic ductal adenocarcinomas (PDAs) overexpress mucin 1 (MUC1), a transmembrane mucin glycoprotein. MUC1(high) PDA patients also express high levels of cyclooxygenase 2 (COX-2) and show poor prognosis. The cytoplasmic tail of MUC1 (MUC1-CT) partakes in oncogenic signaling, resulting in accelerated cancer progression. Our aim was to understand the regulation of Cox-2 expression by MUC1.
Levels of COX-2 and MUC1 were determined in MUC1(-/-), MUC1(low), and MUC1(high) PDA cells and tumors using reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry. Proliferative and invasive potential was assessed using MTT and Boyden chamber assays. Chromatin immunoprecipitation was performed to evaluate binding of MUC1-CT to the promoter of COX-2 gene.
Significantly higher levels of COX-2 mRNA and protein were detected in MUC1(high) versus MUC1(low/null) cells, which were recapitulated in vivo. In addition, deletion of MUC1 gene and transient knockdown of MUC1 led to decreased COX-2 level. Also, MUC1-CT associated with the COX-2 promoter at ∼1000 base pairs upstream of the transcription start site, the same gene locus where nuclear factor κB p65 associates with the COX-2 promoter.
Data supports a novel regulation of COX-2 gene by MUC1 in PDA, the intervention of which may lead to a better therapeutic targeting in PDA patients.</abstract><cop>United States</cop><pub>Lippincott Williams & Wilkins</pub><pmid>26035123</pmid><doi>10.1097/MPA.0000000000000371</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0885-3177 |
| ispartof | Pancreas, 2015-08, Vol.44 (6), p.909-917 |
| issn | 0885-3177 1536-4828 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4500655 |
| source | MEDLINE; Journals@Ovid Complete |
| subjects | Animals Antineoplastic Agents - pharmacology Binding Sites Carcinoma, Pancreatic Ductal - drug therapy Carcinoma, Pancreatic Ductal - enzymology Carcinoma, Pancreatic Ductal - genetics Carcinoma, Pancreatic Ductal - pathology Cell Line, Tumor Cell Movement Cell Proliferation - drug effects Cyclooxygenase 2 - genetics Cyclooxygenase 2 - metabolism Cyclooxygenase 2 Inhibitors - pharmacology Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans Mice, Nude Mucin-1 - genetics Mucin-1 - metabolism Neoplasm Invasiveness Original Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - enzymology Pancreatic Neoplasms - genetics Pancreatic Neoplasms - pathology Promoter Regions, Genetic RNA Interference RNA, Messenger - metabolism Transcription Factor RelA - metabolism Transfection Xenograft Model Antitumor Assays |
| title | Mucin 1 Regulates Cox-2 Gene 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=2025-01-21T11%3A52%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mucin%201%20Regulates%20Cox-2%20Gene%20in%20Pancreatic%20Cancer&rft.jtitle=Pancreas&rft.au=Nath,%20Sritama&rft.date=2015-08-01&rft.volume=44&rft.issue=6&rft.spage=909&rft.epage=917&rft.pages=909-917&rft.issn=0885-3177&rft.eissn=1536-4828&rft_id=info:doi/10.1097/MPA.0000000000000371&rft_dat=%3Cproquest_pubme%3E1696186334%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1696186334&rft_id=info:pmid/26035123&rfr_iscdi=true |