The internally truncated LRP5 receptor presents a therapeutic target in breast cancer
Breast cancer is a common malignant disease, which may be caused by a number of genes deregulated by genomic or epigenomic events. Deregulated WNT/beta-catenin signaling with accumulation of beta-catenin is common in breast tumors, but mutations in WNT signaling pathway components have been rare. An...
Gespeichert in:
| Veröffentlicht in: | PloS one 2009-01, Vol.4 (1), p.e4243-e4243 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e4243 |
|---|---|
| container_issue | 1 |
| container_start_page | e4243 |
| container_title | PloS one |
| container_volume | 4 |
| creator | Björklund, Peyman Svedlund, Jessica Olsson, Anna-Karin Akerström, Göran Westin, Gunnar |
| description | Breast cancer is a common malignant disease, which may be caused by a number of genes deregulated by genomic or epigenomic events. Deregulated WNT/beta-catenin signaling with accumulation of beta-catenin is common in breast tumors, but mutations in WNT signaling pathway components have been rare. An aberrantly spliced internally truncated LRP5 receptor (LRP5Delta666-809, LRP5Delta) was shown recently to be resistant to DKK1 inhibition, and was required for beta-catenin accumulation in hyperparathyroid tumors and parathyroid tumor growth.
Here we show, by reverse transcription PCR and Western blot analysis, that LRP5Delta is frequently expressed in breast tumors of different cancer stage (58-100%), including carcinoma in situ and metastatic carcinoma. LRP5Delta was required in MCF7 breast cancer cells for the non-phosphorylated active beta-catenin level, transcription activity of beta-catenin, cell growth in vitro, and breast tumor growth in a xenograft SCID mouse model. WNT3 ligand, but not WNT1 and WNT3A augmented the endogenous beta-catenin activity of MCF7 cells in a DKK1-insensitive manner. Furthermore, an anti-LRP5 antibody attenuated beta-catenin activity, inhibited cell growth, and induced apoptosis in LRP5Delta-positive MCF7 and T-47D breast cancer cells, but not in control cells.
Our results suggest that the LRP5Delta receptor is strongly implicated in mammary gland tumorigenesis and that its aberrant expression present an early event during disease progression. LRP5 antibody therapy may have a significant role in the treatment of breast cancer. |
| doi_str_mv | 10.1371/journal.pone.0004243 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1289670430</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A473424985</galeid><doaj_id>oai_doaj_org_article_a1bab74ea6844335a5b09a460948c50d</doaj_id><sourcerecordid>A473424985</sourcerecordid><originalsourceid>FETCH-LOGICAL-c698t-8621679f24583b3a9a90a50d7947c395499a4bafdba2a9245d7b5b2e909b283a3</originalsourceid><addsrcrecordid>eNqNk12L1DAUhoso7rr6D0QLwoLIjGk-2uRGGNavgYGVdXdvw2l6OtOl03STVN1_b2an6lS8kF6kJM_7JuflnCR5npF5xors7Y0dXAftvLcdzgkhnHL2IDnOFKOznBL28OD_KHni_Q0hgsk8f5wcZSoTUglxnFxdbjBtuoA7r_YuDW7oDASs0tXFF5E6NNgH69Leoccu-BTSsEEHPQ6hMWkAt8YQDdLSIfiQGugMuqfJoxpaj8_G9SS5-vjh8uzzbHX-aXm2WM1MrmSYyZxmeaFqyoVkJQMFioAgVaF4YZgSXCngJdRVCRRUpKqiFCVFRVRJJQN2krzc-_at9XpMxOuMSpUXhDMSieWeqCzc6N41W3B32kKj7zesW2twsZIWNWQllAVHyCXnjAkQJYn350RxaeKrotebvZf_jv1QTtzeN9eLe7dh0FIyRSP9bnzbUG6xMjE9B-1END3pmo1e22-a5rQochkNTkcDZ28H9EFvG2-wbaFDO3idR0YSWkTw1V_gv5OY76k1xGKbrrbxVhO_CreNiU1UN3F_wQsWO0lJEQWvJ4LIBPwR1jB4r5dfL_6fPb-esqcH7AahDRtv29hPtvNTkO9B46z3Duvf4WVE72bgV516NwN6nIEoe3EY_B_R2PTsJ8OBAf0</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1289670430</pqid></control><display><type>article</type><title>The internally truncated LRP5 receptor presents a therapeutic target in breast cancer</title><source>MEDLINE</source><source>PMC (PubMed Central)</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Free Full-Text Journals in Chemistry</source><creator>Björklund, Peyman ; Svedlund, Jessica ; Olsson, Anna-Karin ; Akerström, Göran ; Westin, Gunnar</creator><contributor>Ouchi, Toru</contributor><creatorcontrib>Björklund, Peyman ; Svedlund, Jessica ; Olsson, Anna-Karin ; Akerström, Göran ; Westin, Gunnar ; Ouchi, Toru</creatorcontrib><description>Breast cancer is a common malignant disease, which may be caused by a number of genes deregulated by genomic or epigenomic events. Deregulated WNT/beta-catenin signaling with accumulation of beta-catenin is common in breast tumors, but mutations in WNT signaling pathway components have been rare. An aberrantly spliced internally truncated LRP5 receptor (LRP5Delta666-809, LRP5Delta) was shown recently to be resistant to DKK1 inhibition, and was required for beta-catenin accumulation in hyperparathyroid tumors and parathyroid tumor growth.
Here we show, by reverse transcription PCR and Western blot analysis, that LRP5Delta is frequently expressed in breast tumors of different cancer stage (58-100%), including carcinoma in situ and metastatic carcinoma. LRP5Delta was required in MCF7 breast cancer cells for the non-phosphorylated active beta-catenin level, transcription activity of beta-catenin, cell growth in vitro, and breast tumor growth in a xenograft SCID mouse model. WNT3 ligand, but not WNT1 and WNT3A augmented the endogenous beta-catenin activity of MCF7 cells in a DKK1-insensitive manner. Furthermore, an anti-LRP5 antibody attenuated beta-catenin activity, inhibited cell growth, and induced apoptosis in LRP5Delta-positive MCF7 and T-47D breast cancer cells, but not in control cells.
Our results suggest that the LRP5Delta receptor is strongly implicated in mammary gland tumorigenesis and that its aberrant expression present an early event during disease progression. LRP5 antibody therapy may have a significant role in the treatment of breast cancer.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0004243</identifier><identifier>PMID: 19158955</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Accumulation ; Analysis ; Animals ; Antibodies ; Apoptosis ; beta Catenin - metabolism ; Breast cancer ; Breast Neoplasms - metabolism ; Breast Neoplasms - therapy ; Cancer ; Carcinoma - metabolism ; Cell Biology/Cell Signaling ; Cell Biology/Gene Expression ; Cell Line, Tumor ; Colorectal cancer ; Deregulation ; Development and progression ; Dkk1 protein ; Female ; Gene Expression Regulation, Neoplastic ; Health aspects ; Hospitals ; Humans ; Hyperparathyroidism ; Immunotherapy ; Inhibition ; LDL-Receptor Related Proteins - chemistry ; LDL-Receptor Related Proteins - metabolism ; LDL-Receptor Related Proteins - physiology ; Ligands ; Low Density Lipoprotein Receptor-Related Protein-5 ; LRP5 protein ; Mammary gland ; MEDICIN ; MEDICINE ; Metastases ; Metastasis ; Mice ; Mice, SCID ; Mutation ; Neoplasm Transplantation ; Neuroendocrine tumors ; Oncology/Breast Cancer ; Parathyroid ; Phosphorylation ; Receptors, LDL - metabolism ; Reverse transcription ; Signal transduction ; Stem cells ; Tumorigenesis ; Tumors ; Wnt protein ; Wnt Proteins - metabolism ; Wnt3 Protein ; Wnt3A Protein ; Xenografts ; β-Catenin</subject><ispartof>PloS one, 2009-01, Vol.4 (1), p.e4243-e4243</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Björklund et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (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>Björklund et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c698t-8621679f24583b3a9a90a50d7947c395499a4bafdba2a9245d7b5b2e909b283a3</citedby><cites>FETCH-LOGICAL-c698t-8621679f24583b3a9a90a50d7947c395499a4bafdba2a9245d7b5b2e909b283a3</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/PMC2627768/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627768/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19158955$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-88392$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><contributor>Ouchi, Toru</contributor><creatorcontrib>Björklund, Peyman</creatorcontrib><creatorcontrib>Svedlund, Jessica</creatorcontrib><creatorcontrib>Olsson, Anna-Karin</creatorcontrib><creatorcontrib>Akerström, Göran</creatorcontrib><creatorcontrib>Westin, Gunnar</creatorcontrib><title>The internally truncated LRP5 receptor presents a therapeutic target in breast cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Breast cancer is a common malignant disease, which may be caused by a number of genes deregulated by genomic or epigenomic events. Deregulated WNT/beta-catenin signaling with accumulation of beta-catenin is common in breast tumors, but mutations in WNT signaling pathway components have been rare. An aberrantly spliced internally truncated LRP5 receptor (LRP5Delta666-809, LRP5Delta) was shown recently to be resistant to DKK1 inhibition, and was required for beta-catenin accumulation in hyperparathyroid tumors and parathyroid tumor growth.
Here we show, by reverse transcription PCR and Western blot analysis, that LRP5Delta is frequently expressed in breast tumors of different cancer stage (58-100%), including carcinoma in situ and metastatic carcinoma. LRP5Delta was required in MCF7 breast cancer cells for the non-phosphorylated active beta-catenin level, transcription activity of beta-catenin, cell growth in vitro, and breast tumor growth in a xenograft SCID mouse model. WNT3 ligand, but not WNT1 and WNT3A augmented the endogenous beta-catenin activity of MCF7 cells in a DKK1-insensitive manner. Furthermore, an anti-LRP5 antibody attenuated beta-catenin activity, inhibited cell growth, and induced apoptosis in LRP5Delta-positive MCF7 and T-47D breast cancer cells, but not in control cells.
Our results suggest that the LRP5Delta receptor is strongly implicated in mammary gland tumorigenesis and that its aberrant expression present an early event during disease progression. LRP5 antibody therapy may have a significant role in the treatment of breast cancer.</description><subject>Aberration</subject><subject>Accumulation</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>beta Catenin - metabolism</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - therapy</subject><subject>Cancer</subject><subject>Carcinoma - metabolism</subject><subject>Cell Biology/Cell Signaling</subject><subject>Cell Biology/Gene Expression</subject><subject>Cell Line, Tumor</subject><subject>Colorectal cancer</subject><subject>Deregulation</subject><subject>Development and progression</subject><subject>Dkk1 protein</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hyperparathyroidism</subject><subject>Immunotherapy</subject><subject>Inhibition</subject><subject>LDL-Receptor Related Proteins - chemistry</subject><subject>LDL-Receptor Related Proteins - metabolism</subject><subject>LDL-Receptor Related Proteins - physiology</subject><subject>Ligands</subject><subject>Low Density Lipoprotein Receptor-Related Protein-5</subject><subject>LRP5 protein</subject><subject>Mammary gland</subject><subject>MEDICIN</subject><subject>MEDICINE</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Mutation</subject><subject>Neoplasm Transplantation</subject><subject>Neuroendocrine tumors</subject><subject>Oncology/Breast Cancer</subject><subject>Parathyroid</subject><subject>Phosphorylation</subject><subject>Receptors, LDL - metabolism</subject><subject>Reverse transcription</subject><subject>Signal transduction</subject><subject>Stem cells</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Wnt protein</subject><subject>Wnt Proteins - metabolism</subject><subject>Wnt3 Protein</subject><subject>Wnt3A Protein</subject><subject>Xenografts</subject><subject>β-Catenin</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLwoLIjGk-2uRGGNavgYGVdXdvw2l6OtOl03STVN1_b2an6lS8kF6kJM_7JuflnCR5npF5xors7Y0dXAftvLcdzgkhnHL2IDnOFKOznBL28OD_KHni_Q0hgsk8f5wcZSoTUglxnFxdbjBtuoA7r_YuDW7oDASs0tXFF5E6NNgH69Leoccu-BTSsEEHPQ6hMWkAt8YQDdLSIfiQGugMuqfJoxpaj8_G9SS5-vjh8uzzbHX-aXm2WM1MrmSYyZxmeaFqyoVkJQMFioAgVaF4YZgSXCngJdRVCRRUpKqiFCVFRVRJJQN2krzc-_at9XpMxOuMSpUXhDMSieWeqCzc6N41W3B32kKj7zesW2twsZIWNWQllAVHyCXnjAkQJYn350RxaeKrotebvZf_jv1QTtzeN9eLe7dh0FIyRSP9bnzbUG6xMjE9B-1END3pmo1e22-a5rQochkNTkcDZ28H9EFvG2-wbaFDO3idR0YSWkTw1V_gv5OY76k1xGKbrrbxVhO_CreNiU1UN3F_wQsWO0lJEQWvJ4LIBPwR1jB4r5dfL_6fPb-esqcH7AahDRtv29hPtvNTkO9B46z3Duvf4WVE72bgV516NwN6nIEoe3EY_B_R2PTsJ8OBAf0</recordid><startdate>20090122</startdate><enddate>20090122</enddate><creator>Björklund, Peyman</creator><creator>Svedlund, Jessica</creator><creator>Olsson, Anna-Karin</creator><creator>Akerström, Göran</creator><creator>Westin, Gunnar</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>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DF2</scope><scope>DOA</scope></search><sort><creationdate>20090122</creationdate><title>The internally truncated LRP5 receptor presents a therapeutic target in breast cancer</title><author>Björklund, Peyman ; Svedlund, Jessica ; Olsson, Anna-Karin ; Akerström, Göran ; Westin, Gunnar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c698t-8621679f24583b3a9a90a50d7947c395499a4bafdba2a9245d7b5b2e909b283a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Aberration</topic><topic>Accumulation</topic><topic>Analysis</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>beta Catenin - metabolism</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - therapy</topic><topic>Cancer</topic><topic>Carcinoma - metabolism</topic><topic>Cell Biology/Cell Signaling</topic><topic>Cell Biology/Gene Expression</topic><topic>Cell Line, Tumor</topic><topic>Colorectal cancer</topic><topic>Deregulation</topic><topic>Development and progression</topic><topic>Dkk1 protein</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Health aspects</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Hyperparathyroidism</topic><topic>Immunotherapy</topic><topic>Inhibition</topic><topic>LDL-Receptor Related Proteins - chemistry</topic><topic>LDL-Receptor Related Proteins - metabolism</topic><topic>LDL-Receptor Related Proteins - physiology</topic><topic>Ligands</topic><topic>Low Density Lipoprotein Receptor-Related Protein-5</topic><topic>LRP5 protein</topic><topic>Mammary gland</topic><topic>MEDICIN</topic><topic>MEDICINE</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Mutation</topic><topic>Neoplasm Transplantation</topic><topic>Neuroendocrine tumors</topic><topic>Oncology/Breast Cancer</topic><topic>Parathyroid</topic><topic>Phosphorylation</topic><topic>Receptors, LDL - metabolism</topic><topic>Reverse transcription</topic><topic>Signal transduction</topic><topic>Stem cells</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Wnt protein</topic><topic>Wnt Proteins - metabolism</topic><topic>Wnt3 Protein</topic><topic>Wnt3A Protein</topic><topic>Xenografts</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Björklund, Peyman</creatorcontrib><creatorcontrib>Svedlund, Jessica</creatorcontrib><creatorcontrib>Olsson, Anna-Karin</creatorcontrib><creatorcontrib>Akerström, Göran</creatorcontrib><creatorcontrib>Westin, Gunnar</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 (ProQuest)</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 (ProQuest)</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 China</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>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Uppsala universitet</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>Björklund, Peyman</au><au>Svedlund, Jessica</au><au>Olsson, Anna-Karin</au><au>Akerström, Göran</au><au>Westin, Gunnar</au><au>Ouchi, Toru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The internally truncated LRP5 receptor presents a therapeutic target in breast cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-01-22</date><risdate>2009</risdate><volume>4</volume><issue>1</issue><spage>e4243</spage><epage>e4243</epage><pages>e4243-e4243</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Breast cancer is a common malignant disease, which may be caused by a number of genes deregulated by genomic or epigenomic events. Deregulated WNT/beta-catenin signaling with accumulation of beta-catenin is common in breast tumors, but mutations in WNT signaling pathway components have been rare. An aberrantly spliced internally truncated LRP5 receptor (LRP5Delta666-809, LRP5Delta) was shown recently to be resistant to DKK1 inhibition, and was required for beta-catenin accumulation in hyperparathyroid tumors and parathyroid tumor growth.
Here we show, by reverse transcription PCR and Western blot analysis, that LRP5Delta is frequently expressed in breast tumors of different cancer stage (58-100%), including carcinoma in situ and metastatic carcinoma. LRP5Delta was required in MCF7 breast cancer cells for the non-phosphorylated active beta-catenin level, transcription activity of beta-catenin, cell growth in vitro, and breast tumor growth in a xenograft SCID mouse model. WNT3 ligand, but not WNT1 and WNT3A augmented the endogenous beta-catenin activity of MCF7 cells in a DKK1-insensitive manner. Furthermore, an anti-LRP5 antibody attenuated beta-catenin activity, inhibited cell growth, and induced apoptosis in LRP5Delta-positive MCF7 and T-47D breast cancer cells, but not in control cells.
Our results suggest that the LRP5Delta receptor is strongly implicated in mammary gland tumorigenesis and that its aberrant expression present an early event during disease progression. LRP5 antibody therapy may have a significant role in the treatment of breast cancer.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19158955</pmid><doi>10.1371/journal.pone.0004243</doi><tpages>e4243</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2009-01, Vol.4 (1), p.e4243-e4243 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1289670430 |
| source | MEDLINE; PMC (PubMed Central); DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Aberration Accumulation Analysis Animals Antibodies Apoptosis beta Catenin - metabolism Breast cancer Breast Neoplasms - metabolism Breast Neoplasms - therapy Cancer Carcinoma - metabolism Cell Biology/Cell Signaling Cell Biology/Gene Expression Cell Line, Tumor Colorectal cancer Deregulation Development and progression Dkk1 protein Female Gene Expression Regulation, Neoplastic Health aspects Hospitals Humans Hyperparathyroidism Immunotherapy Inhibition LDL-Receptor Related Proteins - chemistry LDL-Receptor Related Proteins - metabolism LDL-Receptor Related Proteins - physiology Ligands Low Density Lipoprotein Receptor-Related Protein-5 LRP5 protein Mammary gland MEDICIN MEDICINE Metastases Metastasis Mice Mice, SCID Mutation Neoplasm Transplantation Neuroendocrine tumors Oncology/Breast Cancer Parathyroid Phosphorylation Receptors, LDL - metabolism Reverse transcription Signal transduction Stem cells Tumorigenesis Tumors Wnt protein Wnt Proteins - metabolism Wnt3 Protein Wnt3A Protein Xenografts β-Catenin |
| title | The internally truncated LRP5 receptor presents a therapeutic target in breast cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T10%3A22%3A56IST&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=The%20internally%20truncated%20LRP5%20receptor%20presents%20a%20therapeutic%20target%20in%20breast%20cancer&rft.jtitle=PloS%20one&rft.au=Bj%C3%B6rklund,%20Peyman&rft.date=2009-01-22&rft.volume=4&rft.issue=1&rft.spage=e4243&rft.epage=e4243&rft.pages=e4243-e4243&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0004243&rft_dat=%3Cgale_plos_%3EA473424985%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=1289670430&rft_id=info:pmid/19158955&rft_galeid=A473424985&rft_doaj_id=oai_doaj_org_article_a1bab74ea6844335a5b09a460948c50d&rfr_iscdi=true |