Cyclin E Overexpression in Human Mammary Epithelial Cells Promotes Epithelial Cancer-Specific Copy Number Alterations

Cyclin E, a key cell cycle regulatory protein, has been linked to oncogenesis when dysregulated. We have previously shown that overexpression of cyclin E causes replication stress, leading to failure to complete replication at specific chromosomal loci during S phase of the cell cycle. This in turn...

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Published iniScience Vol. 19; pp. 850 - 859
Main Authors Giraldez, Servando, Tamayo, Pablo, Wineinger, Nathan, Kim, William, Reed, Steven I.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 27.09.2019
Elsevier
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ISSN2589-0042
2589-0042
DOI10.1016/j.isci.2019.08.043

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Summary:Cyclin E, a key cell cycle regulatory protein, has been linked to oncogenesis when dysregulated. We have previously shown that overexpression of cyclin E causes replication stress, leading to failure to complete replication at specific chromosomal loci during S phase of the cell cycle. This in turn promotes chromosomal damage during anaphase. Here we show that non-transformed human mammary epithelial cell clones that survive such aberrant mitoses have a specific and reproducible pattern of chromosomal Copy Number Alterations (CNAs) that we have characterized and termed the cyclin E CNA signature. Using a number of computational approaches, we show that this signature resembles one specific CNA pattern enriched in differentiated epithelial-like tumors of the breast and ovary. Analysis of the CNA profile of these clones provides a potential mechanism for cyclin E-mediated oncogenesis. [Display omitted] •Cyclin E overexpression produces a copy number alteration (CNA) signature•Cyclin E signature shows association with features of epithelial-like cancers•Cyclin E signature is reflected in altered patterns of transcription•Cyclin E signature resembles CNA profile in differentiated breast and ovarian cancers Biological Sciences; Molecular Biology; Cell Biology; Cancer; Transcriptomics
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ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2019.08.043