Concluding Remarks
Cyclin E deregulation has been associated with an array of human malignancies. Evidence suggests that the most critical parameter may be deregulation relative to the cell cycle, which can occur if the normal pathway of cyclin E turnover is inactivated. The resulting expression of cyclin E at inappropriate times of the cell cycle can then interfere with efficient progression through both S phase and M phase. Although not yet proven, we propose that these cyclin E-mediated cell cycle perturbations ultimately result in chromosome instability.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ekholm SV, Reed SI (2000) Regulation of G(1) cyclin-dependent kinases in the mammalian cell cycle. Curr Opin Cell Biol 12:676–684.
Ekholm SV, Zickert P, Reed SI, et al (2001) Accumulation of cyclin E is not a prerequisite for passage through the restriction point. Mol Cell Biol 21:3256–3265.
Dulic V, Lees E, Reed SI (1992) Association of human cyclin E with a periodic G1-S phase protein kinase. Science 257:1958–1961.
Koff A, Giordano A, Desai D, et al (1992) Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle. Science 257:1689–1694.
Keyomarsi K, Contc D, Jr., Toyofuku W, et al (1995) Deregulation of cyclin E in breast cancer. Oncogene 11:941–950.
Donnellan R, Chetty R (1999) Cyclin E in human cancers. FASEB J 13:773–780.
Erlanson M, Landberg G (2001) Prognostic implications of p27 and cyclin E protein contents in malignant lymphomas. Leuk Lymphoma 40:461–470.
Li JQ, Miki H, Ohmori M, et al (2001) Expression of cyclin E and cyclin-dependent kinase 2 correlates with metastasis and prognosis in colorectal carcinoma. Hum Pathol 32:945–953.
Porter PL, Malone KE, Heagerty PJ, et al (1997) Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients [see comments]. Nat Med 3:222–225.
Sandhu C, Slingerland J (2000) Deregulation of the cell cycle in cancer. Cancer Detect Prev 24:107–118.
Bortner DM, Rosenberg MP (1997) Induction of mammary gland hyperplasia and carcinomas in transgenic mice expressing human cyclin E. Mol Cell Biol 17:453–459.
Won KA, Reed SI (1996) Activation of cyclin E/CDK2 is coupled to site-specific autophosphorylation and ubiquitin-dependent degradation of cyclin E. Embo J 15:4182–93.
Strohmaier H, Spruck CH, Kaiser P, et al (2001) Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature 413:316–322.
Clurman BE, Sheaff RJ, Thress K, et al (1996) Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation. Genes Dev 10:1979–1990.
Keyomarsi K, Pardee AB (1993) Redundant cyclin overexpression and gene amplification in breast cancer cells. Proc Natl Acad Sci USA 90:1112–6.
Courjal F, Louason G, Speiser P, et al (1996) Cyclin gene amplification and overexpression in breast and ovarian cancers: evidence for the selection of cyclin D1 in breast and cyclin E in ovarian tumors. Int J Cancer 69:247–253.
Becker KF, Keller G, Hoefler H (2000) The use of molecular biology in diagnosis and prognosis of gastric cancer. Surg Oncol 9:5–11.
Tahara E (1995) Genetic alterations in human gastrointestinal cancers. The application to molecular diagnosis. Cancer 75:1410–1417.
Jackson PK, Eldridge AG, Freed E, et al (2000) The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases. Trends Cell Biol 10:429–439.
Kipreos ET, Pagano M (2000) The F-box protein family. Genome Biol 1:REVIEWS3002.
Koepp DM, Schaefer LK, Ye X, et al (2001) Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science 294:173–177.
Moberg KH, Bell DW, Wahrer DC, et al (2001) Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines. Nature 413:311–316.
Spruck C, Strohmaier H, Sangfelt O, et al (2002) hCDC4 Gene mutations in endometrial cancer. Cancer Res 62:4535–4539.
Spruck CH, Won KA, Reed SI (1999) Deregulated cyclin E induces chromosome instability. Nature 401:297–300.
Diffley JF (2001) DNA replication: building the perfect switch. Curr Biol 11:R367–370.
Mendez J, Stillman B (2000) Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis. Mol Cell Biol 20:8602–8612.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer Science+Business Media, Inc.
About this chapter
Cite this chapter
Spruck, C.H. et al. (2005). Deregulation of Cyclin E and Genomic Instability. In: Li, J.J., Li, S.A., Llombart-Bosch, A. (eds) Hormonal Carcinogenesis IV. Springer, Boston, MA. https://doi.org/10.1007/0-387-23761-5_8
Download citation
DOI: https://doi.org/10.1007/0-387-23761-5_8
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-23783-1
Online ISBN: 978-0-387-23761-9
eBook Packages: MedicineMedicine (R0)