Insufficient effect of p27(KIP1) to inhibit cyclin D1 in human esophageal cancer in vitro

The cell cycle is controlled by protein complexes composed of cyclins and c yclin-dependent kinases. p27(KIP1) (p27) is one of the Kip/Cip family cycli n-dependent kinase inhibitory proteins which negatively regulate cell cycle progression, and have been proposed as candidate tumor suppressor genes. T o examine the role of p27 in the development of human esophageal squamous c ell carcinoma (ESCC), we performed Western blot and immunoprecipitation ana lyses of the levels of expression of p27 protein in a series of ESCC cell l ines. This protein was expressed at various levels in these cell lines duri ng exponential growth, p27 level was significantly associated with that of cyclin D1, but not of cyclin E. Further cell cycle synchronization studies demonstrated that p27 was free or bound with affinity to cyclin E-CDK2 more than to cyclin D1-CDK4 or cyclin D1-CDK6. It is known that overexpression of cyclin D1 rather than cyclin E is involved in the pathogenesis of ESCC. Our findings indicated that high expression of p27 throughout the G1 to S p hase may inhibit more likely cyclin E, than cyclin D1, which promotes tumor growth of esophageal squamous cell carcinoma.