Doxorubicin influences the expression of glucosylceramide synthase in invasive ductal breast cancer
Glucosylceramide synthase (GCS) is one enzyme that provides a major route for ceramide clearance. Recent evidence has indicated an important role for GCS in multidrug resistance (MDR) tumors. Doxorubicin (DOX)can modulate the expression of GCS in leukemia and ovary cell lines. However, few studies h...
Gespeichert in:
| Veröffentlicht in: | PloS one 2012-11, Vol.7 (11), p.e48492-e48492 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e48492 |
|---|---|
| container_issue | 11 |
| container_start_page | e48492 |
| container_title | PloS one |
| container_volume | 7 |
| creator | Zhang, Xiaofang Wu, Xiaojuan Su, Peng Gao, Yongsheng Meng, Bin Sun, Yanlin Li, Li Zhou, Zhiqiang Zhou, Gengyin |
| description | Glucosylceramide synthase (GCS) is one enzyme that provides a major route for ceramide clearance. Recent evidence has indicated an important role for GCS in multidrug resistance (MDR) tumors. Doxorubicin (DOX)can modulate the expression of GCS in leukemia and ovary cell lines. However, few studies have investigated their relationship in breast cancer;
We collected 84 excision biopsies from patients with invasive ductal breast cancer of whom 33 patients had undergone preoperative chemotherapy. Immunohistochemistry was used to analyze the expression of GCS protein and significantly showed that the expression of GCS was higher in the samples from patients treated with preoperative chemotherapy(p = 0.018). In order to investigate the underlying mechanism, breast cancer cell lines were cultured with different concentrations of DOX, and mRNA and protein levels of GCS were then detected;
DOX significantly upregulated the expression of GCS at both the mRNA and protein level in ERα-positive MCF-7 cells.We then block down the Sp1 site of GCS promoter, which inhibited the DOX-mediated increase in GCS expression; and after Erα was inhibited in MCF-7 cells, the up-regulation of GCS by DOX also been inhibited.
In conclusion, our data demonstrated the novel finding that DOX could modulate the expression of GCS through the Sp1 site of GCS promoter in ERα-positive breast cancer cells. |
| doi_str_mv | 10.1371/journal.pone.0048492 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1326736883</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A477093878</galeid><doaj_id>oai_doaj_org_article_eb9e9463fc144277b45394121cfacfe9</doaj_id><sourcerecordid>A477093878</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-b5afb3c3dc1e6ba54c4c38cc0789c92b3e270348e49ab31b55d9582d3a0698373</originalsourceid><addsrcrecordid>eNqNk9uK2zAQhk1p6W7TvkFpDYXSXiS1Drbkm8KyPQUWFnq6FfJ4nGhRrFSSQ_L2VTbeJSl7UXwhI33_P5rRTJa9JMWMMEE-3LjB99rO1q7HWVFwyWv6KDsnNaPTihbs8dH_WfYshJuiKJmsqqfZGWWEsYpV5xl8clvnh8aA6XPTd3bAHjDkcYk5btceQzCuz12XL-wALuwsoNcr02Iedn1c6oD5rXKjg9lg3g4Qtc0bjzrEHHQy88-zJ522AV-M6yT79eXzz8tv06vrr_PLi6spiFLGaVPqrmHAWiBYNbrkwIFJgELIGmraMKSiYFwir3XDSFOWbV1K2jJdVLVkgk2y1wfftXVBjfUJijBaCVZJyRIxPxCt0zdq7c1K-51y2qjbDecXSvtowKLCpsaaV6wDwjkVouElqzmhBDoNHdbJ6-MYbWhW2AL20Wt7Ynp60pulWriNSikIQWUyeDcaePdnwBDVygRAa3WPbkj3JpxJQWkKPMne_IM-nN1ILXRKID2mS3Fhb6ouuBBFnez2YWcPUOlrcWUgNVNn0v6J4P2JIDERt3GhhxDU_Mf3_2evf5-yb4_YJWobl8HZIaaGC6cgP4DgXQgeu_sik0LtZ-GuGmo_C2qchSR7dfxA96K75md_AW3EBaM</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1326736883</pqid></control><display><type>article</type><title>Doxorubicin influences the expression of glucosylceramide synthase in invasive ductal breast cancer</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Zhang, Xiaofang ; Wu, Xiaojuan ; Su, Peng ; Gao, Yongsheng ; Meng, Bin ; Sun, Yanlin ; Li, Li ; Zhou, Zhiqiang ; Zhou, Gengyin</creator><creatorcontrib>Zhang, Xiaofang ; Wu, Xiaojuan ; Su, Peng ; Gao, Yongsheng ; Meng, Bin ; Sun, Yanlin ; Li, Li ; Zhou, Zhiqiang ; Zhou, Gengyin</creatorcontrib><description>Glucosylceramide synthase (GCS) is one enzyme that provides a major route for ceramide clearance. Recent evidence has indicated an important role for GCS in multidrug resistance (MDR) tumors. Doxorubicin (DOX)can modulate the expression of GCS in leukemia and ovary cell lines. However, few studies have investigated their relationship in breast cancer;
We collected 84 excision biopsies from patients with invasive ductal breast cancer of whom 33 patients had undergone preoperative chemotherapy. Immunohistochemistry was used to analyze the expression of GCS protein and significantly showed that the expression of GCS was higher in the samples from patients treated with preoperative chemotherapy(p = 0.018). In order to investigate the underlying mechanism, breast cancer cell lines were cultured with different concentrations of DOX, and mRNA and protein levels of GCS were then detected;
DOX significantly upregulated the expression of GCS at both the mRNA and protein level in ERα-positive MCF-7 cells.We then block down the Sp1 site of GCS promoter, which inhibited the DOX-mediated increase in GCS expression; and after Erα was inhibited in MCF-7 cells, the up-regulation of GCS by DOX also been inhibited.
In conclusion, our data demonstrated the novel finding that DOX could modulate the expression of GCS through the Sp1 site of GCS promoter in ERα-positive breast cancer cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0048492</identifier><identifier>PMID: 23133636</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Analysis ; Anthracyclines ; Antibiotics, Antineoplastic - pharmacology ; Apoptosis ; Biology ; Biotechnology ; Breast cancer ; Cancer ; Cancer therapies ; Carcinoma, Ductal, Breast - drug therapy ; Carcinoma, Ductal, Breast - enzymology ; Care and treatment ; Cell culture ; Cell Line, Tumor ; Ceramide ; Ceramide glucosyltransferase ; Chemotherapy ; Doxorubicin ; Doxorubicin - pharmacology ; Enzymes ; Estrogen Receptor alpha - metabolism ; Female ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Glucosyltransferases - biosynthesis ; Humans ; Immunohistochemistry ; Immunohistochemistry - methods ; Invasiveness ; Leukemia ; Medical research ; Medicine ; Microbial drug resistance ; Middle Aged ; mRNA ; Multidrug resistance ; Pathology ; Patients ; Promoter Regions, Genetic ; Proteins ; RNA ; RNA, Messenger - metabolism ; Sp1 protein ; Tumor cell lines ; Tumors</subject><ispartof>PloS one, 2012-11, Vol.7 (11), p.e48492-e48492</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Zhang et al 2012 Zhang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-b5afb3c3dc1e6ba54c4c38cc0789c92b3e270348e49ab31b55d9582d3a0698373</citedby><cites>FETCH-LOGICAL-c758t-b5afb3c3dc1e6ba54c4c38cc0789c92b3e270348e49ab31b55d9582d3a0698373</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/PMC3487728/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487728/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23133636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Xiaofang</creatorcontrib><creatorcontrib>Wu, Xiaojuan</creatorcontrib><creatorcontrib>Su, Peng</creatorcontrib><creatorcontrib>Gao, Yongsheng</creatorcontrib><creatorcontrib>Meng, Bin</creatorcontrib><creatorcontrib>Sun, Yanlin</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Zhou, Zhiqiang</creatorcontrib><creatorcontrib>Zhou, Gengyin</creatorcontrib><title>Doxorubicin influences the expression of glucosylceramide synthase in invasive ductal breast cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Glucosylceramide synthase (GCS) is one enzyme that provides a major route for ceramide clearance. Recent evidence has indicated an important role for GCS in multidrug resistance (MDR) tumors. Doxorubicin (DOX)can modulate the expression of GCS in leukemia and ovary cell lines. However, few studies have investigated their relationship in breast cancer;
We collected 84 excision biopsies from patients with invasive ductal breast cancer of whom 33 patients had undergone preoperative chemotherapy. Immunohistochemistry was used to analyze the expression of GCS protein and significantly showed that the expression of GCS was higher in the samples from patients treated with preoperative chemotherapy(p = 0.018). In order to investigate the underlying mechanism, breast cancer cell lines were cultured with different concentrations of DOX, and mRNA and protein levels of GCS were then detected;
DOX significantly upregulated the expression of GCS at both the mRNA and protein level in ERα-positive MCF-7 cells.We then block down the Sp1 site of GCS promoter, which inhibited the DOX-mediated increase in GCS expression; and after Erα was inhibited in MCF-7 cells, the up-regulation of GCS by DOX also been inhibited.
In conclusion, our data demonstrated the novel finding that DOX could modulate the expression of GCS through the Sp1 site of GCS promoter in ERα-positive breast cancer cells.</description><subject>Adult</subject><subject>Aged</subject><subject>Analysis</subject><subject>Anthracyclines</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Biotechnology</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Carcinoma, Ductal, Breast - drug therapy</subject><subject>Carcinoma, Ductal, Breast - enzymology</subject><subject>Care and treatment</subject><subject>Cell culture</subject><subject>Cell Line, Tumor</subject><subject>Ceramide</subject><subject>Ceramide glucosyltransferase</subject><subject>Chemotherapy</subject><subject>Doxorubicin</subject><subject>Doxorubicin - pharmacology</subject><subject>Enzymes</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Glucosyltransferases - biosynthesis</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunohistochemistry - methods</subject><subject>Invasiveness</subject><subject>Leukemia</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Microbial drug resistance</subject><subject>Middle Aged</subject><subject>mRNA</subject><subject>Multidrug resistance</subject><subject>Pathology</subject><subject>Patients</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins</subject><subject>RNA</subject><subject>RNA, Messenger - metabolism</subject><subject>Sp1 protein</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9uK2zAQhk1p6W7TvkFpDYXSXiS1Drbkm8KyPQUWFnq6FfJ4nGhRrFSSQ_L2VTbeJSl7UXwhI33_P5rRTJa9JMWMMEE-3LjB99rO1q7HWVFwyWv6KDsnNaPTihbs8dH_WfYshJuiKJmsqqfZGWWEsYpV5xl8clvnh8aA6XPTd3bAHjDkcYk5btceQzCuz12XL-wALuwsoNcr02Iedn1c6oD5rXKjg9lg3g4Qtc0bjzrEHHQy88-zJ522AV-M6yT79eXzz8tv06vrr_PLi6spiFLGaVPqrmHAWiBYNbrkwIFJgELIGmraMKSiYFwir3XDSFOWbV1K2jJdVLVkgk2y1wfftXVBjfUJijBaCVZJyRIxPxCt0zdq7c1K-51y2qjbDecXSvtowKLCpsaaV6wDwjkVouElqzmhBDoNHdbJ6-MYbWhW2AL20Wt7Ynp60pulWriNSikIQWUyeDcaePdnwBDVygRAa3WPbkj3JpxJQWkKPMne_IM-nN1ILXRKID2mS3Fhb6ouuBBFnez2YWcPUOlrcWUgNVNn0v6J4P2JIDERt3GhhxDU_Mf3_2evf5-yb4_YJWobl8HZIaaGC6cgP4DgXQgeu_sik0LtZ-GuGmo_C2qchSR7dfxA96K75md_AW3EBaM</recordid><startdate>20121102</startdate><enddate>20121102</enddate><creator>Zhang, Xiaofang</creator><creator>Wu, Xiaojuan</creator><creator>Su, Peng</creator><creator>Gao, Yongsheng</creator><creator>Meng, Bin</creator><creator>Sun, Yanlin</creator><creator>Li, Li</creator><creator>Zhou, Zhiqiang</creator><creator>Zhou, Gengyin</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>DOA</scope></search><sort><creationdate>20121102</creationdate><title>Doxorubicin influences the expression of glucosylceramide synthase in invasive ductal breast cancer</title><author>Zhang, Xiaofang ; Wu, Xiaojuan ; Su, Peng ; Gao, Yongsheng ; Meng, Bin ; Sun, Yanlin ; Li, Li ; Zhou, Zhiqiang ; Zhou, Gengyin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-b5afb3c3dc1e6ba54c4c38cc0789c92b3e270348e49ab31b55d9582d3a0698373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Analysis</topic><topic>Anthracyclines</topic><topic>Antibiotics, Antineoplastic - pharmacology</topic><topic>Apoptosis</topic><topic>Biology</topic><topic>Biotechnology</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Carcinoma, Ductal, Breast - drug therapy</topic><topic>Carcinoma, Ductal, Breast - enzymology</topic><topic>Care and treatment</topic><topic>Cell culture</topic><topic>Cell Line, Tumor</topic><topic>Ceramide</topic><topic>Ceramide glucosyltransferase</topic><topic>Chemotherapy</topic><topic>Doxorubicin</topic><topic>Doxorubicin - pharmacology</topic><topic>Enzymes</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Glucosyltransferases - biosynthesis</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunohistochemistry - methods</topic><topic>Invasiveness</topic><topic>Leukemia</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Microbial drug resistance</topic><topic>Middle Aged</topic><topic>mRNA</topic><topic>Multidrug resistance</topic><topic>Pathology</topic><topic>Patients</topic><topic>Promoter Regions, Genetic</topic><topic>Proteins</topic><topic>RNA</topic><topic>RNA, Messenger - metabolism</topic><topic>Sp1 protein</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Xiaofang</creatorcontrib><creatorcontrib>Wu, Xiaojuan</creatorcontrib><creatorcontrib>Su, Peng</creatorcontrib><creatorcontrib>Gao, Yongsheng</creatorcontrib><creatorcontrib>Meng, Bin</creatorcontrib><creatorcontrib>Sun, Yanlin</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Zhou, Zhiqiang</creatorcontrib><creatorcontrib>Zhou, Gengyin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>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>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Xiaofang</au><au>Wu, Xiaojuan</au><au>Su, Peng</au><au>Gao, Yongsheng</au><au>Meng, Bin</au><au>Sun, Yanlin</au><au>Li, Li</au><au>Zhou, Zhiqiang</au><au>Zhou, Gengyin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Doxorubicin influences the expression of glucosylceramide synthase in invasive ductal breast cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-11-02</date><risdate>2012</risdate><volume>7</volume><issue>11</issue><spage>e48492</spage><epage>e48492</epage><pages>e48492-e48492</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Glucosylceramide synthase (GCS) is one enzyme that provides a major route for ceramide clearance. Recent evidence has indicated an important role for GCS in multidrug resistance (MDR) tumors. Doxorubicin (DOX)can modulate the expression of GCS in leukemia and ovary cell lines. However, few studies have investigated their relationship in breast cancer;
We collected 84 excision biopsies from patients with invasive ductal breast cancer of whom 33 patients had undergone preoperative chemotherapy. Immunohistochemistry was used to analyze the expression of GCS protein and significantly showed that the expression of GCS was higher in the samples from patients treated with preoperative chemotherapy(p = 0.018). In order to investigate the underlying mechanism, breast cancer cell lines were cultured with different concentrations of DOX, and mRNA and protein levels of GCS were then detected;
DOX significantly upregulated the expression of GCS at both the mRNA and protein level in ERα-positive MCF-7 cells.We then block down the Sp1 site of GCS promoter, which inhibited the DOX-mediated increase in GCS expression; and after Erα was inhibited in MCF-7 cells, the up-regulation of GCS by DOX also been inhibited.
In conclusion, our data demonstrated the novel finding that DOX could modulate the expression of GCS through the Sp1 site of GCS promoter in ERα-positive breast cancer cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23133636</pmid><doi>10.1371/journal.pone.0048492</doi><tpages>e48492</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-11, Vol.7 (11), p.e48492-e48492 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1326736883 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Aged Analysis Anthracyclines Antibiotics, Antineoplastic - pharmacology Apoptosis Biology Biotechnology Breast cancer Cancer Cancer therapies Carcinoma, Ductal, Breast - drug therapy Carcinoma, Ductal, Breast - enzymology Care and treatment Cell culture Cell Line, Tumor Ceramide Ceramide glucosyltransferase Chemotherapy Doxorubicin Doxorubicin - pharmacology Enzymes Estrogen Receptor alpha - metabolism Female Gene expression Gene Expression Profiling Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Glucosyltransferases - biosynthesis Humans Immunohistochemistry Immunohistochemistry - methods Invasiveness Leukemia Medical research Medicine Microbial drug resistance Middle Aged mRNA Multidrug resistance Pathology Patients Promoter Regions, Genetic Proteins RNA RNA, Messenger - metabolism Sp1 protein Tumor cell lines Tumors |
| title | Doxorubicin influences the expression of glucosylceramide synthase in invasive ductal breast cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T18%3A34%3A41IST&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=Doxorubicin%20influences%20the%20expression%20of%20glucosylceramide%20synthase%20in%20invasive%20ductal%20breast%20cancer&rft.jtitle=PloS%20one&rft.au=Zhang,%20Xiaofang&rft.date=2012-11-02&rft.volume=7&rft.issue=11&rft.spage=e48492&rft.epage=e48492&rft.pages=e48492-e48492&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0048492&rft_dat=%3Cgale_plos_%3EA477093878%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=1326736883&rft_id=info:pmid/23133636&rft_galeid=A477093878&rft_doaj_id=oai_doaj_org_article_eb9e9463fc144277b45394121cfacfe9&rfr_iscdi=true |