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- Title
Growth regulation by p27<sup>Kip1</sup> is abrogated by multiple mechanisms in aggressive malignant lymphomas.
- Authors
Lin, Zhaosheng; Lim, Steve; Lim, Megan S.
- Abstract
Summary. The cyclin-dependent kinase inhibitor p27Kip1 is a key regulator of the G1 /S transition, and an inverse relationship between p27Kip1 protein expression and proliferation index has been reported in malignant lymphomas. However, a subset of aggressive B-cell lymphomas demonstrates high p27Kip1 expression despite a high proliferation index. The aim of this study was to determine potential mechanisms by which lymphoma cells abrogate the growth inhibitory effect of high p27Kip1 . The effect of transforming growth factor-β (TGF-β) and serum stimulation on p27Kip1 expression and cyclin E/cdk2 activity was investigated in four lymphoma cell lines, Jurkat, CEM-6, OCI-Ly1 and Nalm-6. Reactive lymphocytes responded to growth inhibitory TGF-β by inducing p27Kip1 expression, with subsequent accumulation of cells in G0 /G1 . In contrast, TGF-β did not alter the level of p27Kip1 in Jurkat, CEM-6 and OCI-Ly1 cells with no change in cyclin E/cdk2-kinase activity. Serum stimulation also did not result in a significant change in p27Kip1 expression. Western blot analysis of subcellular fractions demonstrated cytoplasmic p27Kip1 , corroborated by immunocytochemistry in a subset of the lymphoma cells. Sequestration of p27Kip1 by cyclin D3 was observed in the nuclear and cytoplasmic fractions of Nalm-6, OCI-Ly-1 and NCEB cells. These results indicate that multiple mechanisms contribute to the abrogation of growth regulation by unscheduled high p27Kip1 protein expression including deficient response to TGF-β and serum, sequestration by cyclin D3 and cytoplasmic displacement.
- Subjects
LYMPHOMAS; CYCLIN-dependent kinases; GROWTH regulators
- Publication
British Journal of Haematology, 2003, Vol 121, Issue 5, p739
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1046/j.1365-2141.2003.04354.x