Elevated 4N (G2-tetraploid) cell populations are unstable intermediates in the development of many human cancers. However, 4N cell populations are intermixed with larger diploid fractions in vivo, limiting investigation of these key intermediates of neoplastic progression. Therefore, to study elevated 4N cell populations in human neoplasia, we used flow cytometry to purify populations of spontaneously arising TP53wt and TP53mut 4N cells from cell strains derived from premalignant Barrett's esophagus biopsies. Using oligonucleotide arrays, we identified 625 genes differentially expressed in at least one replicate 2N/4N comparison in each strain and in hTERT-immortalized cultures of the TP53mut strains. Strikingly, when hierarchically clustered, these data contained a large node of 124 genes that were up-regulated in 4N TP53mut cells in the absence of condensed chromosomes. Most of these genes function in G2-M to mediate processes such as chromosome condensation and segregation. These results describe the molecular phenotype of dysregulated G2-M functions and cell cycle checkpoints in a key intermediate of human neoplastic progression.
|Original language||English (US)|
|Number of pages||7|
|State||Published - Jul 15 2003|
ASJC Scopus subject areas
- Cancer Research