Nature Medicine
3, 222 - 225 (1997)
doi:10.1038/nm0297-222
Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patientsPeggy L. Porter1, 5, Kathleen E. Malone2, 6, Patrick J. Heagerty3, 7, Gail M. Alexander1, Laura A. Gatti1, Eduardo J. Firpo4, Janet R. Daling2, 6
& James M. Roberts4
1Program in Cancer Biology, C1-10S, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington, 98109, USA
2Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington 98109, USA
3Program in Biostatistics, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington 98109, USA
4Division of Basic Sciences, Fred Hutchinson Cancer Research Center, School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98109, USA
5Department of Pathology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98109, USA
6Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98109, USA
7Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98109, USA Mutations in certain genes that regulate the cell cycle, such as p16 and p53, are frequently found in human cancers1. However, tumor-specific mutations are uncommon in genes encoding cyclin E and the CDK inhibitor p27Kip1, two cell-cycle regulators that are also thought to contribute to tumor progression2−8. It is now known that levels of both cyclin E and p27 can be controlled by posttranscriptional mechanisms, indicating that expression of these proteins can be altered by means other than simply mutation of their respective genes9,10. Thus, changes in p27 and cyclin E protein levels in tumors might be more common than previously anticipated and may be indicators of tumor behavior.
REFERENCES
- Clurman, B. & Roberts, J. cellcycle and cancer. J. Natl. Cancer Inst. 87, 1499−1501 (1995). | PubMed | ChemPort |
- Pietenpol, J. et al. Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias. Cancer Res. 55, 1206−1210 (1995). | PubMed | ISI | ChemPort |
- Ponce-Castaneda, M. et al. p27Kip1: Chromosomal mapping to 12p12−l2p13 and absence of mutations in human tumors. Cancer Res. 55, 1211−1214 (1995). | PubMed | ChemPort |
- Konstantin, S. et al. p27/Kip1 mutation found in breast cancer. Cancer Res. 56, 2400−2404 (1996). | PubMed | ISI | ChemPort |
- Leach, F. et al. Amplification of cyclin genes in colorectal carcinomas. Cancer Res. 53, 1986−1989 (1993). | PubMed | ISI | ChemPort |
- Keyomarsi, K. et al. Cyclin E, a potential prognostic marker for breast cancer. Cancer Res. 54, 380−385 (1994). | PubMed | ISI | ChemPort |
- Said, T. & Medina, D. Cell cyclins and cyclin-dependent kinase activities in mouse mammary tumor development. Carcinogenesls 16, 823−830 (1995). | ChemPort |
- Fero, M.L. et al. A syndrome of multi-organ hyperplasia with features of gigantism, tumorigenesis and female sterility in p27Kip1−deficient mice. Cell 85, 733−744 (1996). | Article | PubMed | ISI | ChemPort |
- Clurman, B., Sheaff, R., Thress, K., Groudine, M. & Roberts, J. Turnover of cyclin E by the ubiquitin-proteosome pathway is regulated by CDK2 binding and cyclin phosphorylation. Genes Dev. 10, 1979−1990 (1996). | PubMed | ISI | ChemPort |
- Pagano, M. et al. Role of the ubiquitin-proteosome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science 269, 682−685 (1995). | PubMed | ISI | ChemPort |
- Dulic, V., Lees, E. & Reed, S. Association of human cyclin E with a periodic G1−S phase protein kinase. Science 257, 1958−1961 (1992). | PubMed | ISI | ChemPort |
- Koff, A. et al. Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. Cell 66, 1217−1228 (1991). | Article | PubMed | ISI | ChemPort |
- Nourse, J. et al. lnterleukin-2-mediated elimination of p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin. Nature 372, 570−573 (1994). | Article | PubMed | ISI | ChemPort |
- Coats, S., Flannagan, W., Nourse, J. & Roberts, J. Requirement of p27Kip1 for restriction point control of the fibroblast cell cycle. Science 272, 877−880 (1996). | PubMed | ISI | ChemPort |
- McGuire, W. & Clark, G. Prognostic factors and treatment decisions in axillarynode negative breast cancer. N. Engl. J. Med. 326, 1756−1761 (1992). | PubMed | ISI | ChemPort |
- Dutta, A., Chandra, R., Leiter, L. & Lester, S. Cyclins as markers of tumor proliferation: Immunocytochemical studies in breast cancer. Proc. Natl. Acad. Sci. USA 92, 5386−5390 (1995). | PubMed | ChemPort |
- Ohtsubo, M., Theodoras, A., Schumacher, J., Roberts, J. & Pagano, M. Human cyclin E, a nuclear protein essential for the Gl-to-S phase transition. Mol. Cell. Biol. 15, 2612−2624 (1995). | PubMed | ISI | ChemPort |
- Ohtsubo, M. & Roberts, J. Cyclin-dependent regulation of G1 in mammalian fibroblasts. Science 259, 1908−1912 (1993). | PubMed | ISI | ChemPort |
- Gerdes, J., Becker, M. & Key, G. Immunohistological detection of tumour growth fraction (Ki-67 antigen) in formalin-fixed and routinely processed tissues J. Pathol. 168, 85−86 (1992). | PubMed | ISI | ChemPort |
- Lin, D. & Ying, Z. Cox regression with incomplete covariate measurements. J. Am. Statist. Assoc. 88, 1341−1349 (1993). | ISI |
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