Identification of Genes Periodically Expressed in the Human Cell Cycle and Their Expression in Tumors

Abstract

The genome-wide program of gene expression during the cell division cycle in a human cancer cell line (HeLa) was characterized using cDNA microarrays. Transcripts of >850 genes showed periodic variation during the cell cycle. Hierarchical clustering of the expression patterns revealed coexpressed groups of previously well-characterized genes involved in essential cell cycle processes such as DNA replication, chromosome segregation, and cell adhesion along with genes of uncharacterized function. Most of the genes whose expression had previously been reported to correlate with the proliferative state of tumors were found herein also to be periodically expressed during the HeLa cell cycle. However, some of the genes periodically expressed in the HeLa cell cycle do not have a consistent correlation with tumor proliferation. Cell cycle-regulated transcripts of genes involved in fundamental processes such as DNA replication and chromosome segregation seem to be more highly expressed in proliferative tumors simply because they contain more cycling cells. The data in this report provide a comprehensive catalog of cell cycle regulated genes that can serve as a starting point for functional discovery. The full dataset is available at http://genome-www.stanford.edu/Human-CellCycle/HeLa/.

The cell cycle and cancer

“…In a study of 182 breast cancers, the accelerated cell cycle phenotype had a much higher risk of relapse when compared with the out-of-cycle and G 1 -delayed/arrested phenotypes (HR = 3.90, p < 0.001) [110,111]. These early proofof-concept studies, applying the cell cycle phenotype test, are consistent with published gene expression profiling studies showing that conserved tumour expression patterns include many proliferation-associated genes and that increased expression of these so-called 'proliferation signatures' is associated with enhanced malignancy [78,112,113]. It will be of major interest to determine how this simple cell cycle biomarker test, which is highly suited to routine surgical biopsy material, compares with expensive multigene tests such as Oncotype DX [114].…”

Cell cycle dependent TN‐C promoter activity determined by live cell imaging

“…Understanding precisely the role of a gene product, and how its expression is regulated, requires understanding the temporal characteristics of expression, the stochastic fluctuations of that expression, and the influences of processes such as cell growth and cell cycling. Although it is relatively easy to collect a dataset of large numbers of sequential images of live cells on commercial instrumentation, deriving reliable and quantitative data from large numbers of migrating and proliferating cells over long periods of time remains challenging (36,37). The cell segmentation and tracking analysis performed here was based on the phase contrast channel alone.…”

Comparing genomic expression patterns across species identifies shared transcriptional profile in aging

“…For example, the development of methods to systematically assign genes to 'regulons' 37,38 may make possible regulon-based measures of correlation that could be more sensitive and specific in their identification of analogous biological programs. The integrative use of expression data from different species is an emerging area of research [39][40][41][42][43] , and elements of these different approaches might be combined to develop additional tools. Our computational approach is also readily generalized to data on protein expression and modification 44 .…”