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rdf:type |
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lifeskim:mentions |
umls-concept:C0013216,
umls-concept:C0025914,
umls-concept:C0026336,
umls-concept:C0026809,
umls-concept:C0033414,
umls-concept:C0288331,
umls-concept:C0683598,
umls-concept:C1332397,
umls-concept:C1458155,
umls-concept:C1514559,
umls-concept:C2348628
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pubmed:issue |
6
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pubmed:dateCreated |
1999-12-28
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pubmed:abstractText |
Bcl-x(L), a prosurvival member of the Bcl-2 family that is expressed in many tumors, represses apoptosis induced by chemotherapeutic drugs in vitro. However, the contribution of apoptosis and prosurvival Bcl-2-related proteins to chemotherapy resistance in vivo is unknown and has been challenged by recent results with clonogenic survival assays. To test the ability of Bcl-x(L) to provide chemotherapy resistance to tumors, we transfected the mouse bcl-x(L) gene into the tumorigenic SCK mammary cell line and assessed the response of tumor cells to chemotherapeutic drugs in clonogenic assays and in a syngeneic mouse model. Bcl-x(L) conferred protection on SCK cells against methotrexate at certain drug concentrations, but not at all against 5-fluorouracil in clonogenic survival assays in vitro. Injection of SCK cells transfected with Bcl-x(L) or control plasmid in the mammary fat pads of syngeneic recipient mice resulted in tumors of similar size. However, although the volume of control tumors regressed up to 80% after 4 to 5 days of chemotherapy, SCK tumors expressing Bcl-x(L) did not regress and continued to grow in the presence of methotrexate or 5-fluorouracil. In addition, numbers of apoptotic cells were significantly higher in control tumors as compared to Bcl-x(L)-expressing tumors in animals treated with methotrexate or 5-fluorouracil. These results provide evidence that inhibition of apoptosis through Bcl-x(L) overexpression can promote resistance to chemotherapy in tumors in vivo.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-10440760,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-2173928,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-2570548,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-2790800,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-7539458,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-7561089,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-7585531,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-7607090,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-7655019,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-7684624,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-7794804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-7803231,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-8185674,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-8256847,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-8275468,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-8417786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-8467491,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-8481910,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-8547651,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-8623925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-8695785,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-8704213,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-8752171,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9033638,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9049849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9157989,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9217161,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9242521,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9242554,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9256286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9263629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9346240,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9381178,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9443402,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9735050,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9850056,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10595916-9988752
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0002-9440
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
155
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1861-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10595916-Adenocarcinoma,
pubmed-meshheading:10595916-Animals,
pubmed-meshheading:10595916-Antimetabolites, Antineoplastic,
pubmed-meshheading:10595916-Apoptosis,
pubmed-meshheading:10595916-Drug Resistance, Neoplasm,
pubmed-meshheading:10595916-Drug Screening Assays, Antitumor,
pubmed-meshheading:10595916-Female,
pubmed-meshheading:10595916-Fluorouracil,
pubmed-meshheading:10595916-Gene Expression,
pubmed-meshheading:10595916-Mammary Neoplasms, Experimental,
pubmed-meshheading:10595916-Methotrexate,
pubmed-meshheading:10595916-Mice,
pubmed-meshheading:10595916-Neoplasm Transplantation,
pubmed-meshheading:10595916-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:10595916-Transfection,
pubmed-meshheading:10595916-Tumor Cells, Cultured,
pubmed-meshheading:10595916-bcl-X Protein
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pubmed:year |
1999
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pubmed:articleTitle |
Overexpression of Bcl-x(L) promotes chemotherapy resistance of mammary tumors in a syngeneic mouse model.
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pubmed:affiliation |
Department of Obstetrics and Gynecology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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