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Methylation and silencing of the Thrombospondin-1 promoter in human cancer

Oncogene volume 18, pages 3284–3289 (1999)Cite this article

Abstract

Neovascularization is a common feature of many human cancers, but relatively few molecular defects have been demonstrated in genes regulating angiogenesis. Decreased expression of Thrombospondin-1 (THBS1), a P53 and Rb regulated angiogenesis inhibitor, has been observed in some human tumors, including glioblastoma multiforme (GBM). To study whether methylation-associated inactivation is involved in down-regulating THBS1 expression in cancer, we analysed the methylation status of THBS1 in several cell lines and primary tumors. Three cell lines (RKO, CEM and RAJI) were completely methylated at several CpG sites within the THBS1 5′ CpG island, and had no detectable expression by RT – PCR. THBS1 expression was readily reactivated using the methylation-inhibitor 5-deoxy-azacytidine in all three lines. Furthermore, THBS1 methylation was present in 33% (14/42) of primary GBMs. Thus, de novo methylation may serve as a potential way to inactivate THBS1 expression in human neoplasms.

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Acknowledgements

This work was supported in part by a grant from the Brain Tumor Society and NCI grant 5UO1CA64928. The Brain Resource Center of the Johns Hopkins University Alzheimer's Disease Research Center is supported by NIH Grant AG05146. NA is supported by NIH training grant 1-T32-DK07713. J-PI is a Kimmel Foundation Scholar.

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Authors and Affiliations

  1. The Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, MD, 21231, Maryland, USA

    Qing Li, Nita Ahuja, Peter C Burger & Jean-Pierre J Issa

  2. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, 21231, Maryland, MD, USA

    Peter C Burger

  3. Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, 21231, Maryland, MD, USA

    Nita Ahuja

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  1. Qing Li
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Li, Q., Ahuja, N., Burger, P. et al. Methylation and silencing of the Thrombospondin-1 promoter in human cancer. Oncogene 18, 3284–3289 (1999). https://doi.org/10.1038/sj.onc.1202663

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