Rapamycin can restore the negative regulatory function of transforming growth factor beta 1 in high grade lymphomas

Cytokine
Anna SebestyénL Kopper

Abstract

TGF-β1 (transforming growth factor beta 1) is a negative regulator of lymphocytes, inhibiting proliferation and switching on the apoptotic program in normal lymphoid cells. Lymphoma cells often lose their sensitivity to proapoptotic/anti-proliferative regulators such as TGF-β1. Rapamycin can influence both mTOR (mammalian target of rapamycin) and TGF-β signaling, and through these pathways it is able to enhance TGF-β induced anti-proliferative and apoptotic responses. In the present work we investigated the effect of rapamycin and TGF-β1 combination on cell growth and on TGF-β and mTOR signalling events in lymphoma cells. Rapamycin, an inhibitor of mTORC1 (mTOR complex 1) did not elicit apoptosis in lymphoma cells; however, the combination of rapamycin with exogenous TGF-β1 induced apoptosis and restored TGF-β1 dependent apoptotic machinery in several lymphoma cell lines with reduced TGF-β sensitivity in vitro. In parallel, the phosphorylation of p70 ribosomal S6 kinase (p70S6K) and ribosomal S6 protein, targets of mTORC1, was completely eliminated. Knockdown of Smad signalling by Smad4 siRNA had no influence on apoptosis induced by the rapamycin+TGF-β1, suggesting that this effect is independent of Smad signalling. However, ap...Continue Reading

References

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Citations

Aug 2, 2015·Seminars in Cancer Biology·Joseph G Taylor, John G Gribben
Jul 28, 2016·Experimental Eye Research·Cynthia L Pervan
Jul 31, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Noémi NagyAnna Sebestyén
Jun 9, 2018·Pathology Oncology Research : POR·Tamás SticzAnna Sebestyén

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