**5. Dysregulation of cell cycle**

Dysregulation of cell cycle can also results in malignant cell proliferation and Tumorigenesis. Cyclin D1, for example, has been reported to be overexpressed in human breast cancer (18). Observation has been confirmed in MMTV-Ras and MMTV-Neu mice deficit in Cyclin D1. Tumor development completely stops in these animals which show the critical role of Cyclin D1 in Ras-Neu transformation pathway..Although overexpression of Cdc25b make mammary glands hyperplasic and more sensitive to carcinogenic chemicals, it does not directly induce tumorigeneses. Recently, inhibitor of nuclear factor kappa-B kinase (IKK a, a responsible kinase for activation of NF-k B, was identified as a necessary factor for Cyclin D1-associated epithelial proliferation in MMTV-Neu (but not in MMTV- Ra s) mice (11).
