These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Differential effects of transforming growth factor on cell cycle regulatory molecules in human myeloid leukemia cells.
    Author: Hu X, Zhang X, Zhong Q, Fisher AB, Bryington M, Zuckerman KS.
    Journal: Oncogene; 2001 Oct 18; 20(47):6840-50. PubMed ID: 11687963.
    Abstract:
    In this report we have studied the mechanism by which Transforming Growth Factor beta (TGF beta) inhibits growth of human myeloid leukemia cell lines. TGF beta 1 arrested cells in G1 phase and significantly downregulated the expression of cyclin D2, cyclin D3, cdk4, cyclin A, and cdk2. The downregulation of the molecules resulted in approximately 50-90% decrease of the molecule-dependent kinase activity, varying with each molecule. Although treatment of cells with TGF beta 1 up-regulated accumulation of p27(kip1) in both nucleus and cytoplasm, the association of the p27(kip1) with cdk2, cyclin A, cyclin D2, cyclin D3, and cdk4 was markedly down-regulated, suggesting that p27(kip1) is not responsible for the downregulation of the kinase activity. In contrast, TGF beta 1 upregulated cyclin E-associated p27(kip1) with no effect on the expression of cyclin E. p27(kip1)-immunodepletion upregulated cyclin E-dependent kinase activity by more than 10-fold in TGF beta 1-treated cells but not in proliferating cells; whereas immunodepletion of p27(kip1) from cdk2-immunoprecipitates markedly downregulated cdk2 kinase activity in the lysates extracted from both proliferating and TGF beta-treated cells. Consistent with this observation, TGF beta 1 and p27(kip1) antisense cDNA had a synergistic or additive inhibitory effect on cdk2 but not cyclin E-dependent kinase activity. Our data suggest that (1) TGF beta 1-mediated growth inhibition is accomplished through multiple pathways and (2) p27(kip1) has opposing effects on cdk2 and cyclin E activity in response to TGF beta 1.
    [Abstract] [Full Text] [Related] [New Search]