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p27 Kip 1 Expression by Contact Inhibition as a Prognostic Index of Human Glioma
Author(s) -
Fuse Takahisa,
Tanikawa Motoki,
Nakanishi Makoto,
Ikeda Kyoji,
Tada Toyohiro,
Inagaki Hiroshi,
Asai Kiyofumi,
Kato Taiji,
Yamada Kazuo
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741393.x
Subject(s) - glioma , cell growth , cancer research , western blot , growth inhibition , contact inhibition , biology , cell cycle , kinase , cell , proliferation index , microbiology and biotechnology , gene , biochemistry
The clinical manifestations of human glioma are known tobe diverse, ranging from aggressive growth and invasion to apparent dormancy;however, the molecular mechanism underlying this diversity has been largelyunexplored. In the present study, we characterized four human glioma celllines, T98G, A172, U251, and NAC6, each of which has distinct growthproperties. A172 and U251 cells continue to grow after confluency, whereas thegrowth of T98G and NAC6 cells is contact inhibited. Northern and western blotanalyses revealed that at high cell density, the expression of p27 Kip1 cyclin‐dependent kinase inhibitor was dramatically enhanced at boththe RNA and the protein levels in T98G and NAC6 cells but not in A172 or U251.These facts together with the finding that overexpression of p27 Kip1 caused G1 arrest in A172 and T98G cells suggest that the induction ofp27 Kip 1 represents an important determinant of growth at high cell density. Immunohistochemical analyses of 42 primary gliomas revealed an inverse correlation between the level of p27 protein and the Ki‐67 proliferative index. Kaplan‐Meier plots demonstrated that a low level of p27 in tumors is associated with decreased overall survival. Thus, disrupted regulation of p27 expression at high cell density may play an important role in determining the clinical behavior of human gliomas as well as the prognosis for glioma patients.