back to the home pageThe proliferation of mammalian cells by extracellular signals occurs during the G1 phase of the cell cycle. During this period, growth-stimulatory and growth-inhibitory signals transduced from the extracellular environment impinge on the cell cycle apparatus operating in the nucleus. This apparatus, composed of cyclins and their cyclin-dependent kinases, may respond by setting into motion an autonomous cell division program that carries the cells through S, G2 and M phases or, alternatively, by causing exit from the active cell cycle into the quiescent G0 state. Four mammalian G1 cyclins have been described to date: cyclins D1, D2, D3 and cyclin E. The expression of cyclin D1 is rapidly induced following the exposure of cells to mitogens; it's levels rapidly decline after the mitogens have been removed. This, together with a very short half-life of this proteins permits rapid modulation of cyclin D1 levels in response to changes in extracellular environment (1). Cyclin D1 was originally cloned as an oncogene responsible for parathyroid adenomas (2). Subsequently, the aberrant expression of cyclin D1 was documented in several human malignancies. Most striking is the frequent involvement of cyclin D1 in human breast cancers (3).
Early studies reported cyclin D1 gene amplification in 10-15% of mammary carcinomas. When anti-cyclin D1 antibodies became available, it was discovered that the cyclin D1 protein overexpression is found in the majority of human breast cancers (4) The overexpression of cyclin D1 protein correlates with the presence of receptors for ovarian steroids on tumors cells and is usually linked with poor prognosis (3). Recent study demonstrated that overexpression of cyclin D1 distinguishes malignant breast carcinomas from premalignant breast lesions (5). Consistent with the oncogenic role of cyclin D1 are the observation that transgenic mice engineered to overexpress this cyclin in their breast tissue are prone to mammary adenocarcinomas (6).
References
1. Sherr, C.J. Cell 79,551, 1994
2. Motokura et al.. Nature 350, 512, 1991.
3. Schmidt, E. BioEssays 18, 6, 1996.
4. Bartkova J. et al. Int. J. Cancer 57, 353, 1994.
5. Weinstat-Saslow, D. et al., Nature Medicine 1, 1257, 1995
6. Wang, T.C. et al. Nature 369, 669, 1994.
Submitted by Peter Sicinski on February 8, 1996
Whitehead Institute
Nine Cambridge Center
Cambridge, MA 02142
Phone : 617-258 5176 Fax : 617-258 5213
e-mail : sicinski@wi.mit.edu
Contact for further information
Peter Sicinski: e-mail : sicinski@wi.mit.edu
back to the home page