p27(Kip1) expression by contact inhibition as a prognostic index of human glioma

The clinical manifestations of human glioma are known to be diverse, rangin g from aggressive growth and invasion to apparent dormancy; however, the mo lecular mechanism underlying this diversity has been largely unexplored. In the present study, we characterized four human glioma cell lines, T98G, A1 72, U251, and NAC6, each of which has distinct growth properties, A172 and U251 cells continue to grow after confluency, whereas the growth of T98G an d NAC6 cells is contact inhibited. Northern and western blot analyses revea led that at high cell density, the expression of p27(Kip1) cyclin-dependent kinase inhibitor was dramatically enhanced at both the RNA and the protein revels in T98G and NAC6 cells but not in A172 or U251. These facts togethe r with the finding that overexpression of p27(Kip1) caused Gl arrest in A17 2 and T98G cells suggest that the induction of p27(Kip1) represents an impo rtant determinant of growth at high cell density. Immunohistochemical analy ses of 42 primary gliomas revealed an inverse correlation between the level of p27 protein and the Ki-67 proliferative index. Kaplan-Meier plots demon strated that a low level of p27 in tumors is associated with decreased over all survival. Thus, disrupted regulation of p27 expression at high cell den sity may play an important role in determining the clinical behavior of hum an gliomas as well as the prognosis for glioma patients.