|
|
Transforming growth factor-beta effects on
meningioma cell proliferation and signal transduction pathways
Johnson MD, Okediji E, Woodard A.
Department of Pathology, Vanderbilt Medical School, Nashville, TN
37232, USA. mahlon.johnson@mcmail.vanderbilt.edu
The role of transforming growth factor-beta (TGF-beta) in regulation of
meningioma growth and intracellular events transducing its signals are not
established.
In this study, we evaluated the effects of TGF-beta1 on basal meningioma cell
proliferation in 10 primary human meningioma cell cultures and whether
TGF-beta's signals are transduced by the Smad 2/3, MAPK/Erk kinase-1
(MEK-1)-mitogen-activated protein kinase (MAPK), Akt-p70(S6K) or p38-JUNK
pathways in 5.
We also tested whether neutralizing antibodies to TGF-beta alter CSF stimulation
of meningioma cell proliferation.
On average, TGF-beta reduced meningioma cell [3H]-thymidine incorporation to 58%
of controls at 24% and to 61% of controls at 36 h.
TGF-beta inhibition of meningioma cell proliferation was associated with a
suggestion increased phosphorylation of Smad 2/3 in 2 cases and high basal
phosphorylation in 3 but no change in activation of the MEK-1-MAPK, Akt-p70(S6K)
or p38-JUNK pathways.
As shown previously, CSF stimulated meningioma cell proliferation in the 3
cultures tested.
Neutralizing antibody against TGF-beta augmented this stimulation in 2 of 3
cultures.
These findings suggest that TGF-beta exerts a largely inhibitory effect on basal
meningioma proliferation, perhaps in part through Smad 2/3.
PMID: 15015765 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15015765
|
