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 in | iScience Vol. 19; pp. 850 - 859 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
27.09.2019
Elsevier |
Subjects | |
Online Access | Get full text |
ISSN | 2589-0042 2589-0042 |
DOI | 10.1016/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.
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•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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Lead Contact |
ISSN: | 2589-0042 2589-0042 |
DOI: | 10.1016/j.isci.2019.08.043 |