Cyclins and Breast Cancer

The D-type and E-type cyclins control the G1 to S phase transition during normal cell cycle progression and are critical components of steroid- and growth factor-induced mitogenesis in breast epithelial cells. Mammary epithelial cell-specific overexpression of these genes leads to mammary carcinoma, while in cyclin D1-deficient mice mammary gland development is arrested prior to lobuloalveolar development. Cyclin D1 null mice are resistant to mammary carcinoma induced by the neu and ras oncogenes, indicating an essential role for cyclin D1 in the development of some mammary cancers. Cyclin D1 and E1 are commonly overexpressed in primary breast cancer, with some evidence of an association with an adverse patient outcome. This observation may result in part from their ability to confer resistance to endocrine therapies. The functional consequences of cyclin E overexpression in breast cancer are likely related to its role in cell cycle progression, whereas that of cyclin D1 may also be a consequence of a more recently defined role in transcriptional regulation.