[Role of PTEN protein in multidrug resistance of prostate cancer cells].
In a past decade became evident that phosphatidylinositol-3-kinase controlled signal transduction cascade (PI3K/Akt/PTEN/mTOR) is implicated in resistance of tumor cells to anticancer drugs. Another well studied mechanism of multidrug resistance is associated with the activity of drug transporters of ABC superfamily (first of all P-glycoprotein (Pgp), MRP1, BCRP). Several mechanisms of cell defense can be turned on in one cell. The interconnections between different mechanisms involved in drug resistance are poorly studied. In the present study we used PC3 and DU145 human prostate cell lines to show that PTEN functional status determines level of cell resistance to some drugs, it correlates with expression level of MRP1 and BCRP proteins. We showed that Pgp is not involved in development of drug resistance in these cells. Transfection of PTEN into PTEN-deficient PC3 as well as rapamycin treatment caused the inhibition of PI3K/Akt/mTOR signaling and resulted in cell sensitization to the action of doxorubicin and vinblastine. We showed that PTEN transfection leads to the change in expression of MRP1 and BCRP. Our results show that in prostate cancer cells at least two mechanisms of drug resistance are interconnected. PTEN and mTOR signaling were shown: to be involved into regulation of MRP1 and BCRP.
Sherbakova
E A
EA
Stromskaia
T P
TP
Rybalkina
E Iu
EIu
Kalita
O V
OV
Stavrovskaia
A A
AA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D020123:Sirolimus / Q000493:pharmacokinetics; D058570:TOR Serine-Threonine Kinases
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000903:Antibiotics, Antineoplastic; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C116614:ABCG2 protein, human; C546842:MTOR protein, human; C494929:PTEN protein, human; C421109:multidrug resistance-associated protein 1