Down-regulation of T-STAR, a growth inhibitory protein, after SV40-mediated immortalization.
Normal human cells can undergo a limited number of divisions, whereas transformed cells may have an extended life span and can give rise to immortal cells. To isolate genes involved in the immortalization process, gene expression in SV40-transformed preimmortal human fibroblasts was compared with expression in SV40-transformed immortalized fibroblasts using an mRNA differential display. We found that the growth-inhibitory protein testis-signal transduction and activation of RNA (T-STAR) a homologue of cell-cycle regulator Sam68, is strongly down-regulated in immortalized cells. Overexpression of T-STAR in the SV40-transformed immortalized cells resulted in a strong reduction of colony formation, whereas deletion of the RNA-binding domain of T-STAR abrogated this effect. Down-regulation of testis-signal transduction and activation of RNA (T-STAR) expression is found only in immortal cells isolated after a proliferative crisis accompanied with massive cell death. The strict correlation of down-regulation of T-STAR expression only in those immortal cells that arose after a clear proliferative crisis suggests that the loss of T-STAR might be necessary to bypass crisis.
Kool
J
J
Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Centre, Leiden, 2333AL, The Netherlands.
van Zaane
W
W
van der Eb
A J
AJ
Terleth
C
C
D048868:Adaptor Proteins, Signal Transducing; D015153:Blotting, Western; D002452:Cell Count; D002455:Cell Division; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005347:Fibroblasts; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013539:Simian virus 40 / Q000502:physiology*; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C489559:KHDRBS1 protein, human; C118777:KHDRBS3 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins