Breast cancer expresses functional NMDA receptors
We demonstrate here that functional NMDAR1 and NMDAR2 receptors are expressed by Mcf-7 and SKBR3 breast cancer cell lines, and possibly by most or all high-grade breast tumors, and that these receptors are important for the growth of human breast cancer xenografts in mice. RT-PCR demonstrated mRNA f...
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| creator | North, William G Gao, Guohong Memoli, Vincent A Pang, Roy H Lynch, Launa |
| description | We demonstrate here that functional NMDAR1 and NMDAR2 receptors are expressed by Mcf-7 and SKBR3 breast cancer cell lines, and possibly by most or all high-grade breast tumors, and that these receptors are important for the growth of human breast cancer xenografts in mice. RT-PCR demonstrated mRNA for both NMDAR1 and NMDAR2 receptors are expressed in both Mcf-7 and SKBR3 cell lines, and these messages likely have sequences identical to those reported for human mRNAs. Proteins of the expected respective sizes 120 and 170 kD are generated from these mRNAs by the tumor cells. Cell growth was found to be significantly (P < 0.0001) impaired down to 10% of normal growth by the irreversible NMDAR1 antagonists MK-801 and memantine with IC 50s ranging from 600 to >800 µM and from 200 to 300 µM for the two lines. Paradoxically, memantine with a lower binding affinity had the greater influence of the two inhibitors on cell viability. Immunohistochemical examination of high-grade invasive ductal and lobular breast cancer with our polyclonal antibodies against a peptide (-Met-Ser-Ile-Tyr-Ser-Asp-Lys-Ser-Ile-His-) in the extracellular domain of the NMDAR1 receptor gave specific positive staining for the receptor in all 10 cases examined. Positive staining was chiefly concentrated at the membranes of these tumor tissues. No staining with these antibodies was found for normal breast and kidney tissues. When Mcf-7 cells were grown as tumor xenografts in nu/nu mice, the growth of these tumors was completely arrested by daily treatments with MK-801 over 5 days. All of these data point to active NMDAR receptors being expressed by most breast cancers, and having an important influence on their survival. |
| doi_str_mv | 10.1007/s10549-009-0556-1 |
| format | Article |
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RT-PCR demonstrated mRNA for both NMDAR1 and NMDAR2 receptors are expressed in both Mcf-7 and SKBR3 cell lines, and these messages likely have sequences identical to those reported for human mRNAs. Proteins of the expected respective sizes 120 and 170 kD are generated from these mRNAs by the tumor cells. Cell growth was found to be significantly (P < 0.0001) impaired down to 10% of normal growth by the irreversible NMDAR1 antagonists MK-801 and memantine with IC 50s ranging from 600 to >800 µM and from 200 to 300 µM for the two lines. Paradoxically, memantine with a lower binding affinity had the greater influence of the two inhibitors on cell viability. Immunohistochemical examination of high-grade invasive ductal and lobular breast cancer with our polyclonal antibodies against a peptide (-Met-Ser-Ile-Tyr-Ser-Asp-Lys-Ser-Ile-His-) in the extracellular domain of the NMDAR1 receptor gave specific positive staining for the receptor in all 10 cases examined. Positive staining was chiefly concentrated at the membranes of these tumor tissues. No staining with these antibodies was found for normal breast and kidney tissues. When Mcf-7 cells were grown as tumor xenografts in nu/nu mice, the growth of these tumors was completely arrested by daily treatments with MK-801 over 5 days. All of these data point to active NMDAR receptors being expressed by most breast cancers, and having an important influence on their survival.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-009-0556-1</identifier><identifier>PMID: 19784770</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>New York: Boston : Springer US</publisher><subject>Animals ; Antibodies ; Antineoplastic Agents - pharmacology ; Biological and medical sciences ; Breast cancer ; breast neoplasms ; Breast Neoplasms - drug therapy ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cancer research ; Cancer therapies ; Carrier Proteins - antagonists & inhibitors ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival ; Cellular biology ; Dizocilpine Maleate - pharmacology ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Antagonists - pharmacology ; Female ; Gene Expression Regulation, Neoplastic ; Gynecology. Andrology. Obstetrics ; Humans ; Inhibitory Concentration 50 ; Mammary gland diseases ; Medical sciences ; Medicine ; Medicine & Public Health ; Memantine - pharmacology ; Methyl aspartate ; Mice ; Mice, Nude ; Nerve Tissue Proteins - antagonists & inhibitors ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; NMDA receptors ; Oncology ; Preclinical Study ; Proteins ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate - genetics ; Receptors, N-Methyl-D-Aspartate - metabolism ; RNA ; RNA, Messenger - metabolism ; Rodents ; Time Factors ; Tumor Burden ; Tumor growth ; Tumor markers ; Tumors ; Viral antibodies ; Xenograft Model Antitumor Assays</subject><ispartof>Breast cancer research and treatment, 2010-07, Vol.122 (2), p.307-314</ispartof><rights>Springer Science+Business Media, LLC. 2009</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Springer</rights><rights>Springer Science+Business Media, LLC. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c808t-a3dc7c07141f98c4180258298368964b48e11522c8845a88075e9d7a31ed32223</citedby><cites>FETCH-LOGICAL-c808t-a3dc7c07141f98c4180258298368964b48e11522c8845a88075e9d7a31ed32223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-009-0556-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-009-0556-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22943981$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19784770$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>North, William G</creatorcontrib><creatorcontrib>Gao, Guohong</creatorcontrib><creatorcontrib>Memoli, Vincent A</creatorcontrib><creatorcontrib>Pang, Roy H</creatorcontrib><creatorcontrib>Lynch, Launa</creatorcontrib><title>Breast cancer expresses functional NMDA receptors</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>We demonstrate here that functional NMDAR1 and NMDAR2 receptors are expressed by Mcf-7 and SKBR3 breast cancer cell lines, and possibly by most or all high-grade breast tumors, and that these receptors are important for the growth of human breast cancer xenografts in mice. RT-PCR demonstrated mRNA for both NMDAR1 and NMDAR2 receptors are expressed in both Mcf-7 and SKBR3 cell lines, and these messages likely have sequences identical to those reported for human mRNAs. Proteins of the expected respective sizes 120 and 170 kD are generated from these mRNAs by the tumor cells. Cell growth was found to be significantly (P < 0.0001) impaired down to 10% of normal growth by the irreversible NMDAR1 antagonists MK-801 and memantine with IC 50s ranging from 600 to >800 µM and from 200 to 300 µM for the two lines. Paradoxically, memantine with a lower binding affinity had the greater influence of the two inhibitors on cell viability. Immunohistochemical examination of high-grade invasive ductal and lobular breast cancer with our polyclonal antibodies against a peptide (-Met-Ser-Ile-Tyr-Ser-Asp-Lys-Ser-Ile-His-) in the extracellular domain of the NMDAR1 receptor gave specific positive staining for the receptor in all 10 cases examined. Positive staining was chiefly concentrated at the membranes of these tumor tissues. No staining with these antibodies was found for normal breast and kidney tissues. When Mcf-7 cells were grown as tumor xenografts in nu/nu mice, the growth of these tumors was completely arrested by daily treatments with MK-801 over 5 days. All of these data point to active NMDAR receptors being expressed by most breast cancers, and having an important influence on their survival.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Breast cancer</subject><subject>breast neoplasms</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Carrier Proteins - antagonists & inhibitors</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival</subject><subject>Cellular biology</subject><subject>Dizocilpine Maleate - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Memantine - pharmacology</subject><subject>Methyl aspartate</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Nerve Tissue Proteins - antagonists & inhibitors</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>NMDA receptors</subject><subject>Oncology</subject><subject>Preclinical Study</subject><subject>Proteins</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Receptors, N-Methyl-D-Aspartate - genetics</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>RNA</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Time Factors</subject><subject>Tumor Burden</subject><subject>Tumor growth</subject><subject>Tumor markers</subject><subject>Tumors</subject><subject>Viral antibodies</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNk11rFDEUhgdR7Lb6A7zRRfHjZmpOvnMjrPUTql5or0OaObM7ZXayJjNF_70ZZml3RRYJIZA85z0h75uieATkFAhRrxMQwU1JSJ5CyBLuFDMQipWKgrpbzAhIVUpN5FFxnNIVyaAi5n5xBEZprhSZFfA2okv93LvOY5zjr03ElDDN66HzfRM6186_fnm3mEf0uOlDTA-Ke7VrEz7crifFxYf3P84-leffPn4-W5yXXhPdl45VXnmigENttOegCRWaGs2kNpJfco0AglKvNRdOa6IEmko5BlgxSik7Kd5Mupvhco2Vx66PrrWb2Kxd_G2Da-z-Sdes7DJcW67yYJAFXm4FYvg5YOrtukke29Z1GIZkFeeSUmVYJl8dJEEDaGOoIRl9-hd6FYaYXylZQYBxEGSEnk3Q0rVom64O-YJ-1LQLrogAmn07SDEhqZQKxmc4_QeVR4XrxocO6ybv78n-V8Fuhxc7BSt0bb9KoR1G99O-8kFwVxEm0MeQUsT6xjUgdkyunZJrcyDtmFw7uvV41-7bim1UM_B8C7jkXVvHnNgm3XCUGs6MHoXoxKV81C0x3jp0qPuTqah2wbplzMIX32k2lIAWMv8a9geA_Qbc</recordid><startdate>20100701</startdate><enddate>20100701</enddate><creator>North, William G</creator><creator>Gao, Guohong</creator><creator>Memoli, Vincent A</creator><creator>Pang, Roy H</creator><creator>Lynch, Launa</creator><general>Boston : Springer US</general><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>FBQ</scope><scope>IQODW</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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20100701</creationdate><title>Breast cancer expresses functional NMDA receptors</title><author>North, William G ; Gao, Guohong ; Memoli, Vincent A ; Pang, Roy H ; Lynch, Launa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c808t-a3dc7c07141f98c4180258298368964b48e11522c8845a88075e9d7a31ed32223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Breast cancer</topic><topic>breast neoplasms</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Carrier Proteins - antagonists & inhibitors</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival</topic><topic>Cellular biology</topic><topic>Dizocilpine Maleate - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Inhibitory Concentration 50</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Memantine - pharmacology</topic><topic>Methyl aspartate</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Nerve Tissue Proteins - antagonists & inhibitors</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>NMDA receptors</topic><topic>Oncology</topic><topic>Preclinical Study</topic><topic>Proteins</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><topic>Receptors, N-Methyl-D-Aspartate - genetics</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>RNA</topic><topic>RNA, Messenger - metabolism</topic><topic>Rodents</topic><topic>Time Factors</topic><topic>Tumor Burden</topic><topic>Tumor growth</topic><topic>Tumor markers</topic><topic>Tumors</topic><topic>Viral antibodies</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>North, William G</creatorcontrib><creatorcontrib>Gao, Guohong</creatorcontrib><creatorcontrib>Memoli, Vincent A</creatorcontrib><creatorcontrib>Pang, Roy H</creatorcontrib><creatorcontrib>Lynch, Launa</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</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>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>North, William G</au><au>Gao, Guohong</au><au>Memoli, Vincent A</au><au>Pang, Roy H</au><au>Lynch, Launa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Breast cancer expresses functional NMDA receptors</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2010-07-01</date><risdate>2010</risdate><volume>122</volume><issue>2</issue><spage>307</spage><epage>314</epage><pages>307-314</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><coden>BCTRD6</coden><abstract>We demonstrate here that functional NMDAR1 and NMDAR2 receptors are expressed by Mcf-7 and SKBR3 breast cancer cell lines, and possibly by most or all high-grade breast tumors, and that these receptors are important for the growth of human breast cancer xenografts in mice. RT-PCR demonstrated mRNA for both NMDAR1 and NMDAR2 receptors are expressed in both Mcf-7 and SKBR3 cell lines, and these messages likely have sequences identical to those reported for human mRNAs. Proteins of the expected respective sizes 120 and 170 kD are generated from these mRNAs by the tumor cells. Cell growth was found to be significantly (P < 0.0001) impaired down to 10% of normal growth by the irreversible NMDAR1 antagonists MK-801 and memantine with IC 50s ranging from 600 to >800 µM and from 200 to 300 µM for the two lines. Paradoxically, memantine with a lower binding affinity had the greater influence of the two inhibitors on cell viability. Immunohistochemical examination of high-grade invasive ductal and lobular breast cancer with our polyclonal antibodies against a peptide (-Met-Ser-Ile-Tyr-Ser-Asp-Lys-Ser-Ile-His-) in the extracellular domain of the NMDAR1 receptor gave specific positive staining for the receptor in all 10 cases examined. Positive staining was chiefly concentrated at the membranes of these tumor tissues. No staining with these antibodies was found for normal breast and kidney tissues. When Mcf-7 cells were grown as tumor xenografts in nu/nu mice, the growth of these tumors was completely arrested by daily treatments with MK-801 over 5 days. All of these data point to active NMDAR receptors being expressed by most breast cancers, and having an important influence on their survival.</abstract><cop>New York</cop><pub>Boston : Springer US</pub><pmid>19784770</pmid><doi>10.1007/s10549-009-0556-1</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies Antineoplastic Agents - pharmacology Biological and medical sciences Breast cancer breast neoplasms Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Cancer research Cancer therapies Carrier Proteins - antagonists & inhibitors Carrier Proteins - genetics Carrier Proteins - metabolism Cell Line, Tumor Cell Proliferation - drug effects Cell Survival Cellular biology Dizocilpine Maleate - pharmacology Dose-Response Relationship, Drug Excitatory Amino Acid Antagonists - pharmacology Female Gene Expression Regulation, Neoplastic Gynecology. Andrology. Obstetrics Humans Inhibitory Concentration 50 Mammary gland diseases Medical sciences Medicine Medicine & Public Health Memantine - pharmacology Methyl aspartate Mice Mice, Nude Nerve Tissue Proteins - antagonists & inhibitors Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism NMDA receptors Oncology Preclinical Study Proteins Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Receptors, N-Methyl-D-Aspartate - genetics Receptors, N-Methyl-D-Aspartate - metabolism RNA RNA, Messenger - metabolism Rodents Time Factors Tumor Burden Tumor growth Tumor markers Tumors Viral antibodies Xenograft Model Antitumor Assays |
| title | Breast cancer expresses functional NMDA receptors |
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