Regulation of glioblastoma progression by cord blood stem cells is mediated by downregulation of cyclin D1 |
| |
Authors: | Velpula Kiran Kumar Dasari Venkata Ramesh Tsung Andrew J Gondi Christopher S Klopfenstein Jeffrey D Mohanam Sanjeeva Rao Jasti S |
| |
Institution: | Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, United States of America. |
| |
Abstract: | BackgroundThe normal progression of the cell cycle requires sequential expression of
cyclins. Rapid induction of cyclin D1 and its associated binding with
cyclin-dependent kinases, in the presence or absence of mitogenic signals,
often is considered a rate-limiting step during cell cycle progression
through the G1 phase.Methodology/Principal FindingsIn the present study, human umbilical cord blood stem cells (hUCBSC) in
co-cultures with glioblastoma cells (U251 and 5310) not only induced
G0-G1 phase arrest, but also reduced the number of
cells at S and G2-M phases of cell cycle. Cell cycle regulatory
proteins showed decreased expression levels upon treatment with hUCBSC as
revealed by Western and FACS analyses. Inhibition of cyclin D1 activity by
hUCBSC treatment is sufficient to abolish the expression levels of Cdk 4,
Cdk 6, cyclin B1, β-Catenin levels. Our immuno precipitation experiments
present evidence that, treatment of glioma cells with hUCBSC leads to the
arrest of cell-cycle progression through inactivation of both cyclin D1/Cdk
4 and cyclin D1/Cdk 6 complexes. It is observed that hUCBSC, when
co-cultured with glioma cells, caused an increased
G0-G1 phase despite the reduction of
G0-G1 regulatory proteins cyclin D1 and Cdk 4. We
found that this reduction of G0-G1 regulatory
proteins, cyclin D1 and Cdk 4 may be in part compensated by the expression
of cyclin E1, when co-cultured with hUCBSC. Co-localization experiments
under in vivo conditions in nude mice brain xenografts with
cyclin D1 and CD81 antibodies demonstrated, decreased expression of cyclin
D1 in the presence of hUCBSC.Conclusions/SignificanceThis paper elucidates a model to regulate glioma cell cycle progression in
which hUCBSC acts to control cyclin D1 induction and in concert its partner
kinases, Cdk 4 and Cdk 6 by mediating cell cycle arrest at
G0-G1 phase. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|