title: The cdk1-cyclin B complex is involved in everolimus triggered resistance in the PC3 prostate cancer cell line.
abstract: The growth potential of PC3 prostate cancer cells, sensible (PC3(par)) or resistant (PC3(res)) to the mTOR inhibitor everolimus (RAD001) was investigated. Cell growth and proliferation of PC3(res) was similar to that of PC3(par), and late apoptosis increased in PC3(par) but decreased in PC3(res) following treatment with low dosed everolimus. PC3(res) accumulated in the G2/M-phase, accompanied by cdk1, cdk2 and cyclin B elevation. Knocking down cdk1 or cyclin B distinctly blocked the growth activity of PC3(res). One reason for everolimus resistance may be up-regulation of the cdk1-cyclin B complex in prostate cancer cells, leading to enhanced progression towards G2/M.
authors.affiliation: Department of Urology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Tsaur
authors.forename: Jasmina
authors.initials: J
authors.lastname: Makarević
authors.forename: Lukasz
authors.initials: L
authors.lastname: Hudak
authors.forename: Eva
authors.initials: E
authors.lastname: Juengel
authors.forename: Martin
authors.initials: M
authors.lastname: Kurosch
authors.forename: Christoph
authors.initials: C
authors.lastname: Wiesner
authors.forename: Georg
authors.initials: G
authors.lastname: Bartsch
authors.forename: Sebastian
authors.initials: S
authors.lastname: Harder
authors.forename: Axel
authors.initials: A
authors.lastname: Haferkamp
authors.forename: Roman A
authors.initials: RA
authors.lastname: Blaheta
mesh_terms: D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008297:Male; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D019926:Cyclin B; D007166:Immunosuppressive Agents; D046912:Multiprotein Complexes; D000068338:Everolimus; D016203:CDC2 Protein Kinase; D020123:Sirolimus