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Effects of adenovirus-mediated expression of p27Kip1, p21Waf1 and p16INK4A in cell lines derived from t(2;5) anaplastic large cell lymphoma and Hodgkin's disease.
- Source :
-
Leukemia & lymphoma [Leuk Lymphoma] 2002 Jun; Vol. 43 (6), pp. 1323-8. - Publication Year :
- 2002
-
Abstract
- We investigated the response of SUDHL-1 and L428 cells, derived from t(2;5)-anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD), respectively, to recombinant adenoviruses expressing cyclin-dependent kinase inhibitors (CDKIs) p27Kip1 (Adp27), p21Waf1 (Adp21) and p16INK4A (Adp16). Cell cycle analysis of SUDHL-1 cells after 24 h of infection with 200 multiplicity of infection (MOI) of Adp27, Adp21, and Adp16, showed very high levels of cell debris in the subG1 area. The magnitude of cell debris-events was Adp27/Adp21 > Adp16. Cell cycle analysis of L428 cells revealed absence of cell debris and increased G2 phase in all the groups of cells tested as compared to the controls (mock and AdNull). A minimal increase in G1 phase was also evident in cells infected with Adp27 (52%) compared to uninfected cells (43%), AdNull (45%) and to cells infected with Adp21 (37%) and Adp16 (31%). The presence of significant levels of Coxsackie-adenovirus receptor (CAR) on the cell surface of L428 cells excluded the cell membrane-barrier as responsible for the differences in cell observed in response to the recombinant adenovirus-mediated CDKIs expression as compared to SUDHL-1. We also showed that the recombinant adenovirus-mediated cytotoxicity measured as apoptosis was MOI- and vector-dependent in SUDHL-1 cells at lower MOI (100). In conclusion, the therapeutic effect induced by recombinant adenoviruses expressing p27Kip1, p21Waf1 and p16INK4A is cell-dependent in cells derived from selected lymphoid malignancies. Biochemical cellular differences more than cell surface barriers seem to be responsible for differences in response to recombinant adenovirus-mediated expression of cytotoxic genes. Moreover, the cytotoxicity of recombinant adenoviruses expressing p27Kip1, p21Waf1 and p16INK4A may be further explored as a tool for gene therapy of t(2;5)-derived ALCL.
- Subjects :
- Apoptosis
Calcium-Binding Proteins biosynthesis
Calcium-Binding Proteins genetics
Cell Cycle
Cell Cycle Proteins genetics
Cell Cycle Proteins physiology
Cyclin-Dependent Kinase Inhibitor p16 physiology
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
Cyclins genetics
Cyclins physiology
Genes, p16
Genetic Therapy
Hippocalcin
Hodgkin Disease metabolism
Hodgkin Disease virology
Humans
Integrin alphaVbeta3 biosynthesis
Integrin alphaVbeta3 genetics
Lymphoma, Large B-Cell, Diffuse metabolism
Lymphoma, Large B-Cell, Diffuse virology
Neoplasm Proteins genetics
Phosphorylation
Protein Processing, Post-Translational
Recombinant Fusion Proteins biosynthesis
Recombinant Fusion Proteins physiology
Recoverin
Retinoblastoma Protein metabolism
Tumor Cells, Cultured metabolism
Tumor Cells, Cultured virology
Tumor Suppressor Proteins genetics
Tumor Suppressor Proteins physiology
Adenoviruses, Human genetics
Cell Cycle Proteins biosynthesis
Cyclin-Dependent Kinase Inhibitor p16 biosynthesis
Cyclins biosynthesis
Eye Proteins
Gene Expression Regulation, Viral
Genetic Vectors genetics
Hodgkin Disease pathology
Lipoproteins
Lymphoma, Large B-Cell, Diffuse pathology
Neoplasm Proteins biosynthesis
Nerve Tissue Proteins
Tumor Suppressor Proteins biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1042-8194
- Volume :
- 43
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Leukemia & lymphoma
- Publication Type :
- Academic Journal
- Accession number :
- 12153002
- Full Text :
- https://doi.org/10.1080/10428190290021713