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SV40 T antigen increases the expression and activities of p34 cdc2 , cyclin A, and cyclin B prior to immortalization of human diploid fibroblasts
Author(s) -
Chang Ted HungTse,
Schlegel Robert
Publication year - 1996
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19960201)60:2<161::aid-jcb1>3.0.co;2-v
Subject(s) - biology , mitosis , cell cycle , cyclin , carcinogenesis , cyclin b1 , cyclin a , cyclin d , cyclin b , microbiology and biotechnology , antigen , ploidy , cell , genetics , cyclin dependent kinase 1 , cancer , gene
SV40 T antigen induces karyotype instability soon after it is expressed in human diploid fibroblasts and ultimately promotes cell immortalization and tumorigenesis. Protein levels and activities of mitotic cell cycle proteins have been shown to be elevated in several immortal cell lines relative to their normal parental cells, suggesting a possible role for the aberrant regulation of mitosis in karyotype instability. We show here that IMR‐90 human diploid lung fibroblasts expressing the SV40 tumor antigens display increased protein levels and associated enzymatic activities of cyclin A, cyclin B, and p34 cdc2 long before crisis and immortalization. These elevations cannot be explained by faster cell growth or altered cell cycle distributions. Increased protein levels were not totally accounted for by elevated levels of the corresponding mRNA, indicating that T antigen modulates expression at least partially by posttranscriptional mechanisms. These results indicate that perturbation of mitotic regulatory proteins precedes crisis, and imply that altered mitotic control is a direct consequence of T antigen expression rather than an outcome of secondary events associated with immortalization. © 1996 Wiley‐Liss, Inc.