The genetics and biology of tumor suppression by p27/Kip1

The expression of the Cdk inhibitor p27 is reduced in many diverse human cancer types. Importantly, reduced expression or p27 in tumors correlates with poor prognosis for cancer of the breast, lung, prostate, colon, ovary and other tumor types. Our studies, using mouse models, revealed that p27 was a haploinsufficient tumor suppressor in multiple tissues including stomach, small intestine, colon, lung, skin, and ovary. We further showed that loss of p27 cooperates with multiple oncogene and tumor suppressor gene pathways, suggesting that p27 is almost universally involved in cancer progression. Our current studies are focusing on the mechanisms of tumor suppression by p27 and how p27 is misregulated during cancer progression.