Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-1-21
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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...
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
314
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
565-70
pubmed:dateRevised
2004-11-17
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
pubmed:year
2004
pubmed:articleTitle
Annexin-I expression modulates drug resistance in tumor cells.
pubmed:affiliation
Institute of Parasitology, McGill University, Macdonald Campus, Ste-Anne de Bellevue, Que., Canada.
pubmed:publicationType
Journal Article