Sequential overexpression of LRP and MRP but not P-gp 170 in VP16-selected A549 adenocarcinoma cells.
Chemoresistance remains the major obstacle to successful therapy of lung cancer. In order to understand drug resistance mechanisms, the expression of three proteins involved in multidrug resistance (P-gp, MRP and LRP) was studied, using the non-small cell lung cancer (NSCLC) A549 cell line. In addition, 3 levels of resistance were obtained by continuous exposure of cells to etoposide (VP16), which led to a 22-fold increase of the resistance index. The wild-type A549 strongly expressed the LRP protein while MRP protein was found at a moderate level. Induction of resistance paralleled an increase of the expression of the mrp gene and a decrease of the lrp gene; the mdr1 gene was not expressed. Taken together, these results indicate that intrinsically resistant NSCLC cells exhibit a complex pattern of MDR proteins, still susceptible to evolve under treatment. Such a fact would have to be considered in clinical situations.
Institut Jean Godinot, 51056 Reims, France.
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A
Trussardi
G
G
Poitevin
M C
MC
Gorisse
M J
MJ
Faroux
H
H
Bobichon
C
C
Delvincourt
J C
JC
Jardillier
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein