Low molecular weight cyclin E is specific in breast cancer and is associated with mechanisms of tumor progression.
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.
Wingate
Hannah
H
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Puskas
Agnes
A
Duong
Mylinh
M
Bui
Tuyen
T
Richardson
Dana
D
Liu
Yanna
Y
Tucker
Susan L
SL
Van Pelt
Carolyn
C
Meijer
Laurent
L
Hunt
Kelly
K
Keyomarsi
Khandan
K
D014408:Biomarkers, Tumor / Q000378:metabolism*; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002869:Chromosome Aberrations; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D005260:Female; D042822:Genomic Instability; D006801:Humans; D020033:Protein Isoforms / Q000378:metabolism
D014408:Biomarkers, Tumor; D019927:Cyclin E; D020033:Protein Isoforms; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2