Differential response to genotoxic stress in immortalized or transformed human T-lymphotropic virus type I-infected T-cells.
Several alterations in the mechanism of cell cycle control have been observed in human T-lymphotropic virus type I (HTLV-I)-infected cells. Here, it is reported that HTLV-I-infected cells both in their immortalized and transformed phase do not undergo apoptosis following ionizing radiation (IR) treatment. However, when IL-2 withdrawal is combined with genotoxic stress, HTLV-I-infected T-cells in their immortalized phase (IL-2-dependent) undergo apoptosis where as their transformed counterparts (IL-2-independent) do not. These results suggest that, during the transformation process, the HTLV-I-infected T-cells become less sensitive to cell death signals through the acquisition of constitutive activation of the IL-2 receptor pathway. The expression of bcl-2 and bcl-XL proteins, which are known to increase cell survival mediated by IL-2, as well as of p21waf1 and p53, was not substantially different in immortalized and transformed cells following IR. All together, these findings suggest that activation of alternative anti-apoptotic pathways, regulated by IL-2, might be responsible for the differential cell death response observed in immortalized versus transformed HTLV-I-infected T-cells.
Cereseto
A
A
Kislyakova
T
T
Washington Parks
R
R
Nicot
C
C
Franchini
G
G
D017209:Apoptosis / Q000276:immunology / Q000528:radiation effects; D002461:Cell Line, Transformed; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000276:immunology; D015490:HTLV-I Infections / Q000276:immunology / Q000473:pathology*; D015368:Human T-lymphotropic virus 1; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000528:radiation effects / Q000821:virology*; D016159:Tumor Suppressor Protein p53 / Q000276:immunology; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein