A crosstalk imbalance between p27(Kip1) and its interacting molecules enhances breast carcinogenesis.

p27(Kip1) (p27) is an inhibitor of cyclin/cyclin-dependent kinase complexes, the nuclear loss of which indicates poor prognoses in various solid tumors. In breast cancer cells, the p27 expression level usually decreases during tumor development and progression. In addition, p27 cytoplasmic mislocalization has been reported, but the exact molecular mechanisms remain unclear. Studies have indicated that its phosphorylation status is the key regulator and that several signal transduction pathways are involved in the regulation of both the expression and distribution of p27. To further understand the signals involved, the differences in the profiles of interacting proteins between tumor and normal cells should be elucidated. It is well known that p27 has various interacting partners, such as cyclin, cyclin-depend kinases, CRM1, Jab1, SKP2, and Spy1. Assays used to profile these proteins show differing intracellular p27 expression and localization depending on the cell-cycle phase. We hypothesize that the imbalance of crosstalk between p27 and the other molecules involved in the same signaling pathways plays an indispensable role in breast cancer carcinogenesis.