TGF-β Induces growth arrest in Burkitt lymphoma cells via transcriptional repression of E2F-1

Spender, L. C. and Inman, G. J. (2009) TGF-β Induces growth arrest in Burkitt lymphoma cells via transcriptional repression of E2F-1. Journal of Biological Chemistry, 284(3), pp. 1435-1442. (doi: 10.1074/jbc.m808080200) (PMID:19022773)

Abstract

Transforming growth factor-β (TGF-β) is a potent regulator of tissue homeostasis and can act as both a tumor suppressor and a tumor promoter. The ability to induce cell cycle arrest is a major component of the tumor suppressor function of TGF-β. Lung, mammary, and skin epithelial cells exhibit a common minimal cytostatic program in response to TGF-β signaling involving the repression of the growth-promoting factors c-MYC, Id1, Id2, and Id3. Loss of c-MYC expression is a pivotal event in this process, resulting in derepression of the cyclin-dependent kinase inhibitors CDKN1A (p21) and CDKN2B (p15) and ultimately leading to growth arrest. It is not clear, however, which responses are necessary for TGF-β-mediated growth arrest in other cell types. Here, in human Burkitt lymphoma cells transformed by deregulated c-MYC expression, we demonstrate that efficient TGF-β-induced cytostasis can occur despite both maintenance of c-MYC levels and a lack of p21 and p15 induction. TGF-β treatment also results in induction, rather than repression, of Id1 and Id2 expression. In this context, growth arrest correlates with transcriptional repression of E2F-1, and overexpression of E2F-1 in Burkitt lymphoma cells largely overcomes the TGF-β-mediated G1 arrest phenotype. These data indicate that deregulation of c-MYC in lymphoma cells does not overcome the tumor suppressor function of TGF-β and that repression of E2F-1 transcription is sufficient for the efficient induction of cytostasis.

• Item Type: Articles
• Additional Information: This work was supported by Cancer Research UK and an Association for International Cancer Research fellowship (to G. J. I.).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Spender, Dr Lindsay and Inman, Professor Gareth
• Authors: Spender, L. C., and Inman, G. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Biological Chemistry
• Publisher: American Society for Biochemistry and Molecular Biology, Inc.
• ISSN: 0021-9258
• ISSN (Online): 1083-351X
• Published Online: 19 November 2008