We have located links that may give you full text access.
Journal Article
Research Support, Non-U.S. Gov't
TGF-beta receptor kinase inhibitor LY2109761 reverses the anti-apoptotic effects of TGF-beta1 in myelo-monocytic leukaemic cells co-cultured with stromal cells.
British Journal of Haematology 2008 June
Transforming growth factor beta1 (TGF-beta1) is an essential regulator of cell proliferation, survival and apoptosis, depending on the cellular context. TGF-beta1 is also known to affect cell-to-cell interactions between tumour cells and stromal cells. We investigated the role of TGF-beta1 in the survival of myelo-monocytic leukaemia cell lines co-cultured with bone marrow (BM)-derived mesenchymal stem cells (MSC). Treatment with recombinant human (rh)TGF-beta1 inhibited spontaneous and cytarabine-induced apoptosis in U937 cells, most prominently in U937 cells directly attached to MSCs. Conversely, the pro-survival effects of TGF-beta1 were inhibited by LY2109761 or TGF-beta1 neutralizing antibody. rhTGF-beta1 increased pro-survival phosphorylation of Akt, which was inhibited by LY2109761. The combination of rhTGF-beta1 and MSC co-culture induced significant upregulation of C/EBPbeta gene (CEBPB) and protein expression along with increased C/EBPbeta liver-enriched activating protein: liver-enriched inhibitory protein ratio, suggesting the novel role of C/EBPbeta in TGF-beta1-mediated U937 cell survival in the context of stromal cell support. In summary, these results indicate that TGF-beta1 produced by BM stromal cells promotes the survival and chemoresistance of leukaemia cells under the direct cell-to-cell interactions. The blockade of TGF-beta signalling by LY2109761, which effectively inhibited the pro-survival signalling, may enhance the efficacy of chemotherapy against myelo-monocytic leukaemic cells in the BM microenvironment.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
A Guide to the Use of Vasopressors and Inotropes for Patients in Shock.Journal of Intensive Care Medicine 2024 April 14
Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association.Circulation 2024 April 19
Essential thrombocythaemia: A contemporary approach with new drugs on the horizon.British Journal of Haematology 2024 April 9
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app