title: Genetic deletion and pharmacological inhibition of Akt1 isoform attenuates bladder cancer cell proliferation, motility and invasion.
abstract: Isoform specific expression, intracellular localization and function of Akt in bladder cancer are not known. In the current study, we identified Akt1, followed by Akt2 and Akt3 as the predominant Akt isoform in human T24 and UM-UC-3 metastatic bladder cancer cells. Whereas Akt1 is localized at the membrane, cytoplasm and nucleus, Akt2 is solely cytoplasmic and Akt3 is mostly localized in the nucleus in T24 cells. ShRNA-mediated Akt1 knockdown resulted in impaired T24 cell survival, proliferation, colony formation, migration and microinvasion. Whereas pharmacological inhibition of Akt1 resulted in impaired T24 and UM-UC-3 cell motility, viability and proliferation, effect of pharmacological inhibition by Akt2 inhibitor was limited to proliferation in T24, but not UM-UC-3 cells. Our data provide important clues on the therapeutic benefits of targeting Akt1 for bladder cancer therapy.
authors.affiliation: Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA, United States.
authors.forename: Harika
authors.initials: H
authors.lastname: Sabbineni
authors.affiliation: Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA, United States.
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Alwhaibi
authors.affiliation: Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA, United States.
authors.forename: Anna
authors.initials: A
authors.lastname: Goc
authors.affiliation: Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA, United States.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA, United States.
authors.forename: Alanna
authors.initials: A
authors.lastname: Pruitt
authors.affiliation: Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA, United States; Department of Medicine, Vascular Biology Center and Cancer Center, Georgia Regents University, Augusta, GA, United States. Electronic address: sshenoy@gru.edu.
authors.forename: Payaningal R
authors.initials: PR
authors.lastname: Somanath
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: C561680:4-(4-chlorobenzyl)-1-(7H-pyrrolo(2,3-d)pyrimidin-4-yl)piperidin-4-amine; D011743:Pyrimidines; D011758:Pyrroles; D034741:RNA, Small Interfering; C494918:AKT1 protein, human; C494921:AKT2 protein, human; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt1; Akt2; Akt3; Bladder cancer; Invasion; Proliferation