Abstract
Low molecular weight (LMW) isoforms of cyclin E are post-translationally generated in breast cancer cells and are associated with aggressive disease and poor prognosis. In this study, the specificity of LMW cyclin E to cancer cells was determined by measuring cyclin E expression in tumor and non-tumor tissue from 340 breast cancer patients. Our results reveal the LMW isoforms were detected significantly more frequently in breast tumor tissue than in adjacent non-tumor breast tissues (p < 0.0001). The biologic consequences of the LMW isoforms were studied using a non-tumorigenic mammary epithelial cell line transfected with the cyclin E isoforms and resulted in increased clonogenicity, the inability to enter quiescence in response to growth factor deprivation and genomic instability compared to the full-length cyclin E. Biochemical differences between the full-length and the LMW isoforms were also evident. Biacore analyses show that the LMW isoforms have more efficient binding to CDK2 compared to full-length cyclin E, which could account for the unique biologic consequences observed with the expression of LMW cyclin E. The LMW isoforms of cyclin E are tumor specific, and are biochemically and biologically distinct from the full-length cyclin E which could provide a novel role in breast cancer progression.
Original language | English (US) |
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Pages (from-to) | 1062-1068 |
Number of pages | 7 |
Journal | Cell Cycle |
Volume | 8 |
Issue number | 7 |
DOIs | |
State | Published - Apr 1 2009 |
Keywords
- Breast cancer
- Cell cycle
- Cyclin E
- Low molecular weight
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology
MD Anderson CCSG core facilities
- Tissue Biospecimen and Pathology Resource