Apoptosis promoted by up-regulation of TFPT (TCF3 fusion partner) appears p53 independent, cell type restricted and cell density influenced.
The TFPT/FB1 gene was identified because of its involvement in childhood pre-B acute lymphoblastic leukaemia (ALL). Although its specific function is still unclear, Tfpt has been implicated in cell proliferation and induction of programmed cell death (PCD). Given the critical role of PCD in leukemogenesis, we have investigated the responsiveness of different cell lines to TFPT over expression and the consequent induction of PCD by proliferation kinetic analysis, immunolocalization and TUNEL assay. We have also tested the involvement of factors implicated in cell cycle progression and apoptosis, i.e. caspases, p53, Cdc2. Our results indicate that over expression of TFPT promotes caspase 9-dependent apoptosis, nevertheless the apoptotic cascade is engaged only in culture conditions sustaining cell proliferation and different cell lines display differential responsiveness to TFPT induced apoptosis Although p53 is a main regulator of apoptosis in mammalian cells, the Tfpt induced apoptosis appears p53-independent. These results are discussed relatively to the role played by TFPT in leukemogenesis.
Franchini
Chiara
C
Department of Biomolecular Sciences and Biotechnology, University of Milano, Milano, Italy.
Fontana
Floriana
F
Minuzzo
Mario
M
Babbio
Federica
F
Privitera
Enrica
E
D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D004789:Enzyme Activation; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D011485:Protein Binding; D051820:TCF Transcription Factors / Q000378:metabolism*; D058125:Transcription Factor 7-Like 1 Protein; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
D051792:Basic Helix-Loop-Helix Proteins; D020169:Caspases; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D016159:Tumor Suppressor Protein p53; C544912:TCF7L1 protein, human; C118089:TFPT protein, human; C517750:TFPT protein, mouse; C544913:Tcf7l1 protein, mouse