Journal Article

Deregulation of cdc2 gene expression correlates with overexpression of a 110 kDa CCAAT box binding factor in transformed cells.

A Tanimoto, C Y Kao, C C Chang, Y Sasaguri and R Padmanabhan

in Carcinogenesis

Volume 19, issue 10, pages 1735-1741
Published in print October 1998 | ISSN: 0143-3334
Published online October 1998 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/19.10.1735
Deregulation of cdc2 gene expression correlates with overexpression of a 110 kDa CCAAT box binding factor in transformed cells.

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Eukaryotic cell cycle progression is regulated by an orderly and sequential activation of several cyclin-dependent kinases, which phosphorylate key substrates during this process. p34cdc2, the catalytic subunit of cdc2 kinase, is expressed at the late G1/S boundary and is required for the G2-->M phase transition. Transactivation of the human cdc2 promoter by the DNA tumor virus-encoded oncogenic protein SV40 large T antigen is mediated by induction of a novel 110 kDa CCAAT box binding factor (CBF/cdc2). To investigate whether induction of CBF/cdc2 is an intrinsic property of the viral oncoprotein or is a common event during transformation of normal cells, expression of CBF/cdc2 was analyzed in many human tumor cell lines and in rodent cells spontaneously transformed or stably expressing various oncogenes. Our results showed that CBF/cdc2 was overexpressed in all transformed cells examined, including human 293, MCF-7, HeLa and HepG2 cells. Moreover, expression of CBF/cdc2 was elevated in spontaneously transformed rat liver epithelial cells (C4T), but not detectable in the non-tumorigenic parental (RLE) cells. The elevated levels of CBF/cdc2 expression in C4T cells correlated well with increased cdc2 mRNA and p34cdc2 levels. CBF/cdc2 was also overexpressed in a rat liver epithelial cell line (WB) stably transfected with various oncogenes, v-myc, v-Ha-ras and mutated rat neu and v-src. Using an electrophoretic mobility shift assay, specific binding of CBF/cdc2 to the CCAAT box motifs of the human cdc2, cycA and cdc25C promoters was detected, suggesting that transcription of these cell cycle regulatory genes are coordinately activated by CBF/cdc2.

Journal Article.  0 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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