DEREGULATED EXPRESSION OF P27(KIP1) IN HUMAN BREAST CANCERS

Protein complexes composed of cyclins and cyclin-dependent kinases con trol the orderly progression of mammalian cells through the cell cycle , The p27(Kip1) protein belongs to a family of cyclin-dependent kinase -inhibitory proteins that are negative regulators of cell cycle progre ssion and have been proposed as candidate tumor suppressor genes, Howe ver, the p27(Kip1) gene is only rarely mutated in human primary breast carcinomas and breast cancer cell lines, To further address the role of p27(Kip1) in the development of human tumors, we determined by West ern blot analysis the levels of expression of the p27(Kip1) protein in a series of human cancer cell lines and found that this protein is ex pressed at high levels in many of these cell lines, even during expone ntial growth, The levels of p27(Kip1) were significantly associated wi th the levels of cyclins D1 and E. In contrast to the high level of p2 7(Kip1) in breast cancer cell lines, three cell lines established from normal mammary epithelium expressed low levels of this protein, Cell synchronization studies demonstrated deregulation of the expression of p27(Kip1) throughout the cell cycle in two breast cancer cell lines b ut normal regulation in a normal mammary epithelial cell line, Immunoh istochemical studies on p27(Kip1) expression in 52 primary human breas t cancers indicated that this protein was also expressed at relatively high levels in 44% of the tumor samples, but it was barely detectable or undetectable in the remaining 56% of the samples, Additional studi es are required to determine why some breast cancer cells express rela tively high levels of p27(Kip1) despite its known role as an inhibitor of cell cycle progression.