ErbB-2-induced mammary tumor growth: the role of cyclin D1 and p27Kip1.

The neu (c-erbB-2, HER2) proto-oncogene encodes a receptor tyrosine kinase that is a member of an important growth factor receptor family which includes the epidermal growth factor receptor (EGFR, ErbB1), ErbB3 and ErbB4. The neu is found over-expressed in 20-30% of human breast tumors. The c-erbB-2 is sufficient for the induction of mammary tumorigenesis in transgenic mice and the pathology of these mammary tumors strongly resembles human breast cancer. Murine transgenic models engineered to recapitulate human breast cancer provide an excellent and straightforward approach to dissect the molecular mechanisms governing the onset and progression of this disease. The molecular mechanisms by which ErbB-2 transforms cells involves direct effects on components of the cell-cycle regulatory apparatus. Recent studies have demonstrated a key role for components of the cell-cycle, in particular cyclin D1 and p27Kip1 (p27) in the onset and progression of ErbB-2-induced murine mammary tumorigenesis. Such studies have provided further impetus to therapeutics targeting these cell-cycle proteins.