Comparison of the effects of recombinant adenovirus-mediated expression of wild-type p53 and p27Kip1 on cell cycle and apoptosis in SUDHL-1 cells derived from anaplastic large cell lymphoma.
Recombinant adenoviruses expressing wild-type p53 (AdWTp53) and p27KiP1 (Adp27) were used to compare the effects on cell cycle and apoptosis in SUDHL-1 cells derived from human anaplastic large cell lymphoma. Cells infected with AdWTp53 and Adp27 showed high level of wild-type p53 and p27KiP1 expression, respectively. The expression of these proteins resulted in G1 arrest after 24 h of infection. Although the cells persisted in G1 arrest in both cell populations after 48 and 72 h of infection, the level of apoptosis assessed by TUNEL analysis was higher in cells infected with AdWTp53. Interestingly, apoptosis was more pronounced in cells infected with Adp27 after the initial 24 h and reached a steady state at 48 and 72 h. A lower MOI of Adp27 resulted in G1 arrest associated with a low level of apoptosis in SUDHL-1 cells after 48 h of infection. This was correlated with lower expression of p27KiP1. We postulate that the time-lag and the different level of apoptosis occurring in SUDHL-1 cells infected with AdWTp53 and Adp27 are clearly related to the intrinsic biochemical pathways solicited. In this context our study provides a model to investigate these pathways and better understand the biology of this particular lymphoma. Our data also support a potential application of Adp27 for gene therapy of this lymphoma similarly to AdWTp53 as previously shown.
Turturro
F
F
Human Gene Therapy Research Institute, John Stoddard Cancer Center, and Division of Hematology-Oncology, VA Central Iowa Health Care System, Des Moines 50309-3203, USA.
Frist
A Y
AY
Arnold
M D
MD
Pal
A
A
Cook
G A
GA
Seth
P
P
D000256:Adenoviridae; D017209:Apoptosis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D005822:Genetic Vectors; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27