rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2004-1-21
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pubmed:abstractText |
The use of anti-cancer chemotherapy often leads to the rise of multidrug-resistant (MDR) tumors. We have previously reported the overexpression of a 40kDa protein (P-40) in several MDR tumor cell lines. In this report we describe the cloning of a 1.4kb cDNA with an open reading frame of 344 amino acids that encodes the P-40 protein. Analysis of the P-40 amino acid sequence showed it is identical to the human annexin I (Anx-I) protein. The identity of the isolated P-40 cDNA as Anx-I was confirmed by the specific binding of IPM96 mAb to a 40kDa protein following the in vitro expression of P-40 full-length cDNA. Northern blot analysis of total RNA from drug-sensitive and -resistant cells revealed an increase in P-40 (or Anx-I) mRNA in drug-resistant cells relative to drug-sensitive cells. Transfection of Anx-I cDNA into drug-sensitive MCF-7 cells was carried out without further drug selection and showed 2- to 5-fold increase in resistance of transfected cells to adriamycin, melphalan, and etoposide. Conversely, transfection of reverse Anx-I cDNA into SKOV-3 cells decreased the expression of Anx-I without affecting the expression of other members of the annexin family and showed a 3- to 8-fold increase in sensitivity to these drugs. Of interest was the correlation between the presence of Anx-I and MDR in MDA-MB-231 cells when compared to MCF-7 cells. MDA-MB-231 cells show 3- to 20-fold increase in resistance to adriamycin, melphalan, and etoposide in the absence of detectable levels of P-glycoprotein (P-gp1), the multidrug resistance protein (MRP1) or the breast cancer resistance protein (BCRP). Taken together, these results provide the first direct evidence for the role of Anx-I in MDR of tumor cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ABCG2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Annexin A1,
http://linkedlifedata.com/resource/pubmed/chemical/Annexins,
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Alkylating,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Etoposide,
http://linkedlifedata.com/resource/pubmed/chemical/Melphalan,
http://linkedlifedata.com/resource/pubmed/chemical/Multidrug Resistance-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/multidrug resistance-associated...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
314
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
565-70
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:14733945-ATP-Binding Cassette Transporters,
pubmed-meshheading:14733945-Annexin A1,
pubmed-meshheading:14733945-Annexins,
pubmed-meshheading:14733945-Antibiotics, Antineoplastic,
pubmed-meshheading:14733945-Antineoplastic Agents,
pubmed-meshheading:14733945-Antineoplastic Agents, Alkylating,
pubmed-meshheading:14733945-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:14733945-Blotting, Northern,
pubmed-meshheading:14733945-Cell Line, Tumor,
pubmed-meshheading:14733945-Cloning, Molecular,
pubmed-meshheading:14733945-DNA, Complementary,
pubmed-meshheading:14733945-Dose-Response Relationship, Drug,
pubmed-meshheading:14733945-Doxorubicin,
pubmed-meshheading:14733945-Drug Resistance, Neoplasm,
pubmed-meshheading:14733945-Etoposide,
pubmed-meshheading:14733945-Gene Library,
pubmed-meshheading:14733945-HeLa Cells,
pubmed-meshheading:14733945-Humans,
pubmed-meshheading:14733945-Melphalan,
pubmed-meshheading:14733945-Multidrug Resistance-Associated Proteins,
pubmed-meshheading:14733945-Neoplasm Proteins,
pubmed-meshheading:14733945-Open Reading Frames,
pubmed-meshheading:14733945-P-Glycoprotein,
pubmed-meshheading:14733945-Protein Biosynthesis,
pubmed-meshheading:14733945-RNA,
pubmed-meshheading:14733945-Transcription, Genetic,
pubmed-meshheading:14733945-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
Annexin-I expression modulates drug resistance in tumor cells.
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pubmed:affiliation |
Institute of Parasitology, McGill University, Macdonald Campus, Ste-Anne de Bellevue, Que., Canada.
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pubmed:publicationType |
Journal Article
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