Growth-regulated expression of D-type cyclin genes in human diploid fibroblasts

Won, K. A., Xiong, Y., Beach, D., Gilman, M. Z. (1992) Growth-regulated expression of D-type cyclin genes in human diploid fibroblasts. Proc Natl Acad Sci U S A, 89 (20). pp. 9910-4. ISSN 0027-8424 (Print)0027-8424 (Linking)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/1409718

Abstract

The human CCND1 cyclin D1/PRAD1 gene was previously identified by a genetic screen for G1 cyclin function in Saccharomyces cerevisiae and also was identified as the putative BCL1 oncogene. However, its role in human cell proliferation is not known. To determine if expression of human D-type cyclin genes correlates with the state of cell growth, we examined the level of mRNAs for CCND1 and a related gene, CCND3, in normal human diploid fibroblasts (HDF). The levels of both mRNAs decrease upon serum depletion or at high cell densities. Following stimulation of quiescent fibroblasts with serum, the mRNA levels increase gradually to a peak at about 12 hr, prior to the onset of S phase. Induction of cyclin gene expression by serum is reduced concomitantly with the decline in FOS induction in aging HDFs, suggesting a possible relationship to the decrease in the proliferative response to mitogens during cellular senescence. Cycloheximide partially blocks the induction of CCND1 and CCND3 gene expression by serum, suggesting that both de novo protein synthesis-dependent and -independent pathways contribute to induction. Treatment of HDFs with defined growth factors suggests a correlation between CCND mRNA induction and DNA synthesis. However, induction of these genes is not sufficient for the transition from quiescence through G1 into S phase.

Item Type: Paper
Uncontrolled Keywords: Blood Cell Aging *Cell Cycle Cell Transformation, Neoplastic/genetics Culture Media Cyclins/*genetics Gene Expression Regulation Humans In Vitro Techniques RNA, Messenger/genetics Tumor Cells, Cultured
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Cyclins
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
CSHL Authors:
Communities: CSHL labs > Beach lab
Depositing User: Matt Covey
Date Deposited: 22 Sep 2015 19:27
Last Modified: 09 Nov 2017 20:13
PMCID: PMC50243
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31858

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