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Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (1996) 20, 159–167 (Printed in Great Britain)
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
EFSTATHIOS S. GONOSabf1 and DEMETRIOS A. SPANDIDOSac
aNational Hellenic Research Foundation, Department of Biotechnology and Molecular Oncology, 48 Vas. Constantinou Ave. Athens, 11635, Greece
bLudwig Institute for Cancer Research, Courtauld Building, 91 Riding House St, London, W1P 8BT, U.K.
cUniversity of Crete, Medical School, Heraklion, Greece


Abstract

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.


Key words: cdc2, cdc25, cyclin A, immortalization, senescence, SV40 T antigen.

f1To whom correspondence should be addressed.


doi:10.1006/cbir.1996.0020


ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)