PTEN regulates BCRP/ABCG2 and the side population through the PI3K/Akt pathway in chronic myeloid leukemia
A small population of cancer stem cells named the "side population" (SP) has been demonstrated to be responsible for the persistence of many solid tumors. However, the role of the SP in leukemic pathogenesis remains controversial. The resistance of leukemic stem cells to targeted therapies...
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| creator | Huang, Fang-Fang Zhang, Li Wu, Deng-Shu Yuan, Xiao-Yu Yu, Yan-Hui Zhao, Xie-Lan Chen, Fang-Ping Zeng, Hui |
| description | A small population of cancer stem cells named the "side population" (SP) has been demonstrated to be responsible for the persistence of many solid tumors. However, the role of the SP in leukemic pathogenesis remains controversial. The resistance of leukemic stem cells to targeted therapies, such as tyrosine kinase inhibitors (TKIs), results in therapeutic failure or refractory/relapsed disease in chronic myeloid leukemia (CML). The drug pump, ATP-binding cassette sub-family G member 2 (ABCG2), is well known as a specific marker of the SP and could be controlled by several pathways, including the PI3K/Akt pathway. Our data demonstrated that compared with wild-type K562 cells, the higher percentage of ABCG2+ cells corresponded to the higher SP fraction in K562/ABCG2 (ABCG2 overexpressing) and K562/IMR (resistance to imatinib) cells, which exhibited enhanced drug resistance along with downregulated phosphatase and tensin homologue deleted on chromosome -10 (PTEN) and activated phosphorylated-Akt (p-Akt). PTEN and p-Akt downregulation could be abrogated by both the PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin. Moreover, in CML patients in the accelerated phase/blastic phase (AP/BP), increased SP phenotype rather than ABCG2 expression was accompanied by the loss of PTEN protein and the up-regulation of p-Akt expression. These results suggested that the expression of ABCG2 and the SP may be regulated by PTEN through the PI3K/Akt pathway, which would be a potentially effective strategy for targeting CML stem cells. |
| doi_str_mv | 10.1371/journal.pone.0088298 |
| format | Article |
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However, the role of the SP in leukemic pathogenesis remains controversial. The resistance of leukemic stem cells to targeted therapies, such as tyrosine kinase inhibitors (TKIs), results in therapeutic failure or refractory/relapsed disease in chronic myeloid leukemia (CML). The drug pump, ATP-binding cassette sub-family G member 2 (ABCG2), is well known as a specific marker of the SP and could be controlled by several pathways, including the PI3K/Akt pathway. Our data demonstrated that compared with wild-type K562 cells, the higher percentage of ABCG2+ cells corresponded to the higher SP fraction in K562/ABCG2 (ABCG2 overexpressing) and K562/IMR (resistance to imatinib) cells, which exhibited enhanced drug resistance along with downregulated phosphatase and tensin homologue deleted on chromosome -10 (PTEN) and activated phosphorylated-Akt (p-Akt). PTEN and p-Akt downregulation could be abrogated by both the PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin. Moreover, in CML patients in the accelerated phase/blastic phase (AP/BP), increased SP phenotype rather than ABCG2 expression was accompanied by the loss of PTEN protein and the up-regulation of p-Akt expression. These results suggested that the expression of ABCG2 and the SP may be regulated by PTEN through the PI3K/Akt pathway, which would be a potentially effective strategy for targeting CML stem cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0088298</identifier><identifier>PMID: 24603487</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Adult ; Aged ; AKT protein ; Apoptosis - drug effects ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters - genetics ; ATP-Binding Cassette Transporters - metabolism ; Biology ; Blotting, Western ; Cancer ; Cell Survival - drug effects ; Chromones - pharmacology ; Chronic myeloid leukemia ; Comparative analysis ; Drug resistance ; Enzyme Inhibitors - pharmacology ; Female ; Health aspects ; Homology ; Humans ; Imatinib ; Inhibitors ; K562 Cells ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology ; Male ; Medicine ; Middle Aged ; Mitoxantrone - pharmacology ; Morpholines - pharmacology ; Myeloid leukemia ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Pathogenesis ; Phosphatases ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Phosphatidylinositol 3-Kinases - metabolism ; Protein-tyrosine kinase ; Proto-Oncogene Proteins c-akt - metabolism ; PTEN Phosphohydrolase - genetics ; PTEN Phosphohydrolase - metabolism ; PTEN protein ; Rapamycin ; Reverse Transcriptase Polymerase Chain Reaction ; RNA Interference ; Side-Population Cells - metabolism ; Signal Transduction - drug effects ; Sirolimus - pharmacology ; Solid tumors ; Stem cell transplantation ; Stem cells ; Tensin ; TOR protein ; Tumors ; Tyrosine ; Young Adult</subject><ispartof>PloS one, 2014-03, Vol.9 (3), p.e88298-e88298</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://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>2014 Huang et al 2014 Huang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-9e7443913013afa724e9d566dd47d59d39e6d61e993bc1749e3ae141ab30a5c03</citedby><cites>FETCH-LOGICAL-c758t-9e7443913013afa724e9d566dd47d59d39e6d61e993bc1749e3ae141ab30a5c03</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/PMC3945754/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945754/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24603487$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Viglietto, Giuseppe</contributor><creatorcontrib>Huang, Fang-Fang</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Wu, Deng-Shu</creatorcontrib><creatorcontrib>Yuan, Xiao-Yu</creatorcontrib><creatorcontrib>Yu, Yan-Hui</creatorcontrib><creatorcontrib>Zhao, Xie-Lan</creatorcontrib><creatorcontrib>Chen, Fang-Ping</creatorcontrib><creatorcontrib>Zeng, Hui</creatorcontrib><title>PTEN regulates BCRP/ABCG2 and the side population through the PI3K/Akt pathway in chronic myeloid leukemia</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>A small population of cancer stem cells named the "side population" (SP) has been demonstrated to be responsible for the persistence of many solid tumors. However, the role of the SP in leukemic pathogenesis remains controversial. The resistance of leukemic stem cells to targeted therapies, such as tyrosine kinase inhibitors (TKIs), results in therapeutic failure or refractory/relapsed disease in chronic myeloid leukemia (CML). The drug pump, ATP-binding cassette sub-family G member 2 (ABCG2), is well known as a specific marker of the SP and could be controlled by several pathways, including the PI3K/Akt pathway. Our data demonstrated that compared with wild-type K562 cells, the higher percentage of ABCG2+ cells corresponded to the higher SP fraction in K562/ABCG2 (ABCG2 overexpressing) and K562/IMR (resistance to imatinib) cells, which exhibited enhanced drug resistance along with downregulated phosphatase and tensin homologue deleted on chromosome -10 (PTEN) and activated phosphorylated-Akt (p-Akt). PTEN and p-Akt downregulation could be abrogated by both the PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin. Moreover, in CML patients in the accelerated phase/blastic phase (AP/BP), increased SP phenotype rather than ABCG2 expression was accompanied by the loss of PTEN protein and the up-regulation of p-Akt expression. These results suggested that the expression of ABCG2 and the SP may be regulated by PTEN through the PI3K/Akt pathway, which would be a potentially effective strategy for targeting CML stem cells.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Adult</subject><subject>Aged</subject><subject>AKT protein</subject><subject>Apoptosis - drug effects</subject><subject>ATP Binding Cassette Transporter, Sub-Family G, Member 2</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>Biology</subject><subject>Blotting, Western</subject><subject>Cancer</subject><subject>Cell Survival - drug effects</subject><subject>Chromones - pharmacology</subject><subject>Chronic myeloid leukemia</subject><subject>Comparative analysis</subject><subject>Drug resistance</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Female</subject><subject>Health aspects</subject><subject>Homology</subject><subject>Humans</subject><subject>Imatinib</subject><subject>Inhibitors</subject><subject>K562 Cells</subject><subject>Leukemia</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology</subject><subject>Male</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Mitoxantrone - pharmacology</subject><subject>Morpholines - pharmacology</subject><subject>Myeloid leukemia</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Pathogenesis</subject><subject>Phosphatases</subject><subject>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Protein-tyrosine kinase</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>PTEN Phosphohydrolase - metabolism</subject><subject>PTEN protein</subject><subject>Rapamycin</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA Interference</subject><subject>Side-Population Cells - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Sirolimus - pharmacology</subject><subject>Solid tumors</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Tensin</subject><subject>TOR protein</subject><subject>Tumors</subject><subject>Tyrosine</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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>eNqNk1Fv0zAQxyMEYmPwDRBEQkLw0M6O7Th-mdRVY1RMrBqDV8uNL4m7NA5xAvTb47TZ1KA9ID_Yuvvd_-w7XxC8xmiKCcena9s1lSqnta1gilCSRCJ5EhxjQaJJHCHy9OB8FLxwbo0QI0kcPw-OIhojQhN-HKyXtxdfwwbyrlQtuPB8frM8nZ3PL6NQVTpsCwid0RDWtu4JYytva2yXFzvfckG-nM7u2rBWbfFbbUNThan3VyYNN1sordFhCd0dbIx6GTzLVOng1bCfBN8_XdzOP0-uri8X89nVJOUsaScCOKVEYIIwUZniEQWhWRxrTblmQhMBsY4xCEFWKeZUAFGAKVYrghRLETkJ3u5169I6OZTJScwQ5RwnEfXEYk9oq9aybsxGNVtplZE7g21yqZrWpCVIyjTnDGuNKNAkhRVKsKKZQpHQEeHKa50N2brVBnQKVduociQ69lSmkLn9JYmgjLP-Mh8Ggcb-7MC1cmNcCmWpKrDd7t4sYtz316Pv_kEff91A5co_wFSZ9XnTXlTOKE84p762npo-Qvmlfa9S_6cy4-2jgI-jAM-08KfNVeecXHy7-X_2-seYfX_AFqDKtnC27Pq_5sYg3YNpY51rIHsoMkayH4n7ash-JOQwEj7szWGDHoLuZ4D8BZ4RBDg</recordid><startdate>20140306</startdate><enddate>20140306</enddate><creator>Huang, Fang-Fang</creator><creator>Zhang, Li</creator><creator>Wu, Deng-Shu</creator><creator>Yuan, Xiao-Yu</creator><creator>Yu, Yan-Hui</creator><creator>Zhao, Xie-Lan</creator><creator>Chen, Fang-Ping</creator><creator>Zeng, Hui</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>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>DOA</scope></search><sort><creationdate>20140306</creationdate><title>PTEN regulates BCRP/ABCG2 and the side population through the PI3K/Akt pathway in chronic myeloid leukemia</title><author>Huang, Fang-Fang ; Zhang, Li ; Wu, Deng-Shu ; Yuan, Xiao-Yu ; Yu, Yan-Hui ; Zhao, Xie-Lan ; Chen, Fang-Ping ; Zeng, Hui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-9e7443913013afa724e9d566dd47d59d39e6d61e993bc1749e3ae141ab30a5c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Adult</topic><topic>Aged</topic><topic>AKT protein</topic><topic>Apoptosis - 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pharmacology</topic><topic>Morpholines - pharmacology</topic><topic>Myeloid leukemia</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Pathogenesis</topic><topic>Phosphatases</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Protein-tyrosine kinase</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>PTEN Phosphohydrolase - genetics</topic><topic>PTEN Phosphohydrolase - metabolism</topic><topic>PTEN protein</topic><topic>Rapamycin</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA Interference</topic><topic>Side-Population Cells - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Sirolimus - pharmacology</topic><topic>Solid tumors</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Tensin</topic><topic>TOR protein</topic><topic>Tumors</topic><topic>Tyrosine</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Fang-Fang</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Wu, Deng-Shu</creatorcontrib><creatorcontrib>Yuan, Xiao-Yu</creatorcontrib><creatorcontrib>Yu, Yan-Hui</creatorcontrib><creatorcontrib>Zhao, Xie-Lan</creatorcontrib><creatorcontrib>Chen, Fang-Ping</creatorcontrib><creatorcontrib>Zeng, Hui</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 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 (ProQuest)</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 - 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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>Huang, Fang-Fang</au><au>Zhang, Li</au><au>Wu, Deng-Shu</au><au>Yuan, Xiao-Yu</au><au>Yu, Yan-Hui</au><au>Zhao, Xie-Lan</au><au>Chen, Fang-Ping</au><au>Zeng, Hui</au><au>Viglietto, Giuseppe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PTEN regulates BCRP/ABCG2 and the side population through the PI3K/Akt pathway in chronic myeloid leukemia</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-03-06</date><risdate>2014</risdate><volume>9</volume><issue>3</issue><spage>e88298</spage><epage>e88298</epage><pages>e88298-e88298</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>A small population of cancer stem cells named the "side population" (SP) has been demonstrated to be responsible for the persistence of many solid tumors. However, the role of the SP in leukemic pathogenesis remains controversial. The resistance of leukemic stem cells to targeted therapies, such as tyrosine kinase inhibitors (TKIs), results in therapeutic failure or refractory/relapsed disease in chronic myeloid leukemia (CML). The drug pump, ATP-binding cassette sub-family G member 2 (ABCG2), is well known as a specific marker of the SP and could be controlled by several pathways, including the PI3K/Akt pathway. Our data demonstrated that compared with wild-type K562 cells, the higher percentage of ABCG2+ cells corresponded to the higher SP fraction in K562/ABCG2 (ABCG2 overexpressing) and K562/IMR (resistance to imatinib) cells, which exhibited enhanced drug resistance along with downregulated phosphatase and tensin homologue deleted on chromosome -10 (PTEN) and activated phosphorylated-Akt (p-Akt). PTEN and p-Akt downregulation could be abrogated by both the PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin. Moreover, in CML patients in the accelerated phase/blastic phase (AP/BP), increased SP phenotype rather than ABCG2 expression was accompanied by the loss of PTEN protein and the up-regulation of p-Akt expression. These results suggested that the expression of ABCG2 and the SP may be regulated by PTEN through the PI3K/Akt pathway, which would be a potentially effective strategy for targeting CML stem cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24603487</pmid><doi>10.1371/journal.pone.0088298</doi><tpages>e88298</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-03, Vol.9 (3), p.e88298-e88298 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1504771824 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase Adult Aged AKT protein Apoptosis - drug effects ATP Binding Cassette Transporter, Sub-Family G, Member 2 ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - metabolism Biology Blotting, Western Cancer Cell Survival - drug effects Chromones - pharmacology Chronic myeloid leukemia Comparative analysis Drug resistance Enzyme Inhibitors - pharmacology Female Health aspects Homology Humans Imatinib Inhibitors K562 Cells Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology Male Medicine Middle Aged Mitoxantrone - pharmacology Morpholines - pharmacology Myeloid leukemia Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Pathogenesis Phosphatases Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - metabolism Protein-tyrosine kinase Proto-Oncogene Proteins c-akt - metabolism PTEN Phosphohydrolase - genetics PTEN Phosphohydrolase - metabolism PTEN protein Rapamycin Reverse Transcriptase Polymerase Chain Reaction RNA Interference Side-Population Cells - metabolism Signal Transduction - drug effects Sirolimus - pharmacology Solid tumors Stem cell transplantation Stem cells Tensin TOR protein Tumors Tyrosine Young Adult |
| title | PTEN regulates BCRP/ABCG2 and the side population through the PI3K/Akt pathway in chronic myeloid leukemia |
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