The role of cdc2, cdc25 and cyclin A genes in the maintenance of immortalization and growth arrest in a rat embryonic fibroblast conditional cell line.
Immortalization of rodent cells by oncogenes is a complex biological process which involves the abnormal regulation of genes who control cellular proliferation. The role of the cell cycle control genes cdc2, cdc25 and cyclin A in the maintenance of immortalization and in growth arrest was examined in the tsa14, a SV40 T antigen rat embryonic fibroblast conditional for growth cell line. Analysis of RNA expression showed minimal levels of cdc2 mRNA in both proliferating and growth-arrested tsa14 cells. In contrast, cyclin A mRNA was found downregulated in growth-arrested tsa14 cells, as well as in senescent primary rat embryonic fibroblasts (REFS). The ability of cdc2, or cdc25, or cyclin A genes to maintain the tsa14 immortal phenotype was also examined by electroporations of these genes into the tsa14 cells. Clones over-expressing the electroporated cdc2, or cdc25, or cyclin A, or combinations of these genes growth arrested at the non-permissive conditions similar to controls, thereby suggesting that the expression of these genes alone is insufficient for tsa14 maintenance of immortalization.
Gonos
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ES
National Hellenic Research Foundation, Department of Biotechnology and Molecular Oncology, Athens, Greece.
Spandidos
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D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D016203:CDC2 Protein Kinase / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002461:Cell Line, Transformed / Q000502:physiology; D016922:Cellular Senescence / Q000235:genetics; D016213:Cyclins / Q000235:genetics*; D018274:Electroporation; D005333:Fetus / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000235:genetics; D006131:Growth Inhibitors / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature; D020687:cdc25 Phosphatases
D018797:Cell Cycle Proteins; D016213:Cyclins; D006131:Growth Inhibitors; D012333:RNA, Messenger; D016203:CDC2 Protein Kinase; D010749:Phosphoprotein Phosphatases; D020687:cdc25 Phosphatases; D019204:GTP-Binding Proteins