disruption of the ARF-p53 pathway. Cancer Res 67: 7212–7222. 13. Bagheri-Yarmand R, Biernacka A, Hunt KK, Keyomarsi K (2010) Low molecular weight cyclin E overexpression shortens mitosis, leading to chromosome missegregation and centrosome amplification. Cancer Res 70: 5074–5084. 14. Zhou YJ, Xie YT, Gu J, Yan L, Guan GX, et al. (2011) Overexpression of cyclin E isoforms correlates with poor prognosis in rectal cancer. Eur J Surg Oncol 37: 1078–1084. 15. Corin I, Di Giacomo MC, Lastella P, Bagnulo R, Guanti G, et al. (2006) Tumor-specific hyperac- tive low-molecular-weight cyclin E isoforms detection and characterization in non-metastatic colorectal tumors. Cancer Biol Ther 5: 198–203. 16. Davidson B, Skrede M, Silins I, Shih Ie M, Trope CG, et al. (2007) Low-molecular weight forms of cyclin E differentiate ovarian carcinoma from cells of mesothelial origin and are associated with poor survival in ovarian carcinoma. Cancer 110: 1264–1271. 17. Bales E, Mills L, Milam N, McGahren-Murray M, Bandyopadhyay D, et al. (2005) The low molecular weight cyclin E isoforms augment angiogenesis and metastasis of human melanoma cells in vivo. Cancer Res 65: 692–697. 18. Duong MT, Akli S, Wei C, Wingate HF, Liu W, et al. (2012) LMW-E/CDK2 deregulates acinar morphogenesis, induces tumorigenesis and asso- ciates with the activated b-Raf-ERK1/2-mTOR pathway in breast cancer patients. PLoS Genet 8: e1002538. doi:10.1371/journal.pgen.1002538. 19. Akli S, Van Pelt CS, Bui T, Meijer L, Keyomarsi K (2011) Cdk2 is required for breast cancer mediated by the low-molecular-weight isoform of cyclin E. Cancer Res 71: 3377–3386. 20. Nanos-Webb A, Jabbour NA, Multani AS, Wingate H, Oumata N, et al. (2011) Targeting low molecular weight cyclin E (LMW-E) in breast cancer. Breast Cancer Res TreatE-pub ahead of print 22 June 2011. 21. Spruck C, Sun D, Fiegl H, Marth C, Mueller- Holzner E, et al. (2006) Detection of low molecular weight derivatives of cyclin E1 is a function of cyclin E1 protein levels in breast cancer. Cancer Res 66: 7355–7360. 22. Delk NA, Hunt KK, Keyomarsi K (2009) Altered subcellular localization of tumor-specific cyclin E isoforms affects cyclin-dependent kinase 2 com- plex formation and proteasomal regulation. Cancer Res 69: 2817–2825. 23. Jackman M, Kubota Y, den Elzen N, Hagting A, Pines J (2002) Cyclin A- and cyclin E-Cdk complexes shuttle between the nucleus and the cytoplasm. Mol Biol Cell 13: 1030–1045. 24. Caruso JA, Hunt KK, Keyomarsi K (2010) The neutrophil elastase inhibitor elafin triggers rb- mediated growth arrest and caspase-dependent apoptosis in breast cancer. Cancer Res 70: 7125–7136. PLoS Genetics | www.plosgenetics.org 3 March 2012 | Volume 8 | Issue 3 | e1002623