Prolonged adenovirus-mediated expression of p27(Kip1) unveils unexpected effects of this protein on the phenotype of SUDHL-1 cells derived from t(2;5)-anaplastic large cell lymphoma.
SUDHL-1 cells, derived from human t(2;5)-anaplastic large cell lymphoma (ALCL) were kept in culture for 25 days and analyzed for p27(Kip1)-expression, cell cycle, apoptosis, morphology and phenotype as compared with matched controls at different time points after infection with recombinant adenovirus expressing p27(Kip1) (Adp27). The presence of any change in the cell phenotype occurring during the persistent exogenous expression of p27(Kip1) would be indicative of a "clone" of cells surviving apoptosis by reversing G1 arrest. The level of alpha(nu)beta(5) integrin was completely down regulated in cells infected with Adp27 as assessed by flow cytometry and by immunoprecipitation analysis after 14 days of infection. SUDHL-1 cells regained a significant level of alpha(nu)beta(5) integrin on the cell surface after 25 days of infection with Adp27. Based on the importance of integrins in tumor cell proliferation, we speculate that the down regulation of alpha(nu)beta(5) integrin on the surface of SUDHL-1 cells may represent a less tumorigenic phenotype occurring as a consequence of prolonged expression of p27(Kip1).
Turturro
Francesco
F
Stoddard Cancer Research Institute, Des Moines University, Des Moines, IA 50309, USA. fturtu@lsuhsc.edu
Seth
Prem
P
D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002889:Chromosomes, Human, Pair 2; D002895:Chromosomes, Human, Pair 5; D002999:Clone Cells / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007399:Interphase / Q000187:drug effects; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D019030:Receptors, Vitronectin / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D016023:Integrins; D019030:Receptors, Vitronectin; D025521:Tumor Suppressor Proteins; C064660:integrin alphaVbeta5; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases