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

Leukemia. 2001 Aug;15(8):1225-31. doi: 10.1038/sj.leu.2402181.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenoviridae
  • Apoptosis / genetics*
  • Cell Cycle / genetics*
  • Cell Cycle Proteins / genetics*
  • Cyclin-Dependent Kinase Inhibitor p27
  • Gene Expression Regulation, Neoplastic
  • Genes, p53*
  • Genetic Vectors
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*

Substances

  • Cell Cycle Proteins
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27