EXPRESSION AND REGULATION OF CYCLIN GENES IN BREAST-CANCER

Cyclins, the regulatory subunits of cyclin-dependent kinases, control passage through key checkpoints within the cell cycle. Since dysregulated expression and function of cyclins can lead to loss of normal growth control some of these genes are oncogenes. We have studied cyclin gene expression, regulation and function in breast cancers. Induction of cyclin D1 is an early event in mitogenic stimulation of breast cancer cells by growth factors and steroids. Furthermore, inhibition of cyclin D1 expression is an early response to growth inhibition by antioestrogens. Ectopic expression of cyclin D1 in T-47D breast cancer cells demonstrated that cyclin D1 is rate-limiting for progression through G(1) phase and is sufficient for growth arrested cells to complete the cell cycle. Since this gene is frequently overexpressed in human breast cancers it may contribute to the development and progression of some breast carcinomas.