p27 modulates cell cycle progression and chemosensitivity in human malignant glioma.
The cell cycle regulatory protein p27, an inhibitor of cyclin-dependent kinases (CDK), has been attributed a role in (i) prognosis in breast and colon cancer, (ii) induction of apoptosis in cancer cells, and (iii) resistance to cancer chemotherapy. Here we report that p27 is widely expressed in human malignant gliomas in vivo and in glioma cell lines in vitro. Serum deprivation or confluency promotes p27 protein accumulation in vitro. Neither baseline p27 levels nor p27 levels induced by confluency or serum deprivation correlate with p53 status or drug sensitivity of human glioma cell lines. Expression of antisense p27 mRNA increased the doubling times in T98G glioma cells, whereas sense p27 mRNA had no such effect. There was a density-dependent and drug-specific modulation of chemosensitivity by sense or antisense mRNA expression in T98G cells. Taken together, these data define a strong p27 response to altered growth conditions and suggest a role for p27 in modulating response to chemotherapy in human malignant glioma cells.
Naumann
U
U
Department of Neurology, Eberhard-Karls-University Tübingen, Medical School, Tübingen, Germany.
Weit
S
S
Rieger
L
L
Meyermann
R
R
Weller
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division; D016895:Culture Media, Serum-Free; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors; D015870:Gene Expression; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology*; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases