Report

Low molecular weight cyclin E is specific in breast cancer and is associated with mechanisms of tumor progression

Volume 8, Issue 7   April 1, 2009
Pages 1062 - 1068
http://dx.doi.org/10.4161/cc.8.7.8119
Authors: Hannah Wingate, Agnes Puskas, Mylinh Duong, Tuyen Bui, Dana Richardson, Yanna Liu, Susan L. Tucker, Carolyn Van Pelt, Laurent Meijer, Kelly Hunt and Khandan Keyomarsi

View affiliations

Abstract:
Low molecular weight (LMW) isoforms of cyclin E are posttranslationally 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 was studied using a non-tumorigenic mammary epithelial cell line transfected with the cyclin E isoforms resulting 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 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.

Received: December 18, 2008; Accepted: February 10, 2009

Preview:



Advertisements