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The topoisomerase I- and p53-binding protein topors is differentially expressed in normal and malignant human tissues and may function as a tumor suppressor

Oncogene volume 23, pages 5293–5300 (2004)Cite this article

A Correction to this article was published on 11 July 2019

Abstract

Topors was identified recently as a human protein that binds to topoisomerase I and p53. Topors contains a highly conserved RING domain and localizes in promyelocytic leukemia nuclear bodies. Relatively little is known regarding topors expression patterns or function. We now demonstrate that topors mRNA and protein are widely expressed in normal human tissues. By contrast, topors mRNA and protein levels are decreased or undetectable in colon adenocarcinomas relative to normal colon tissue, and expression of the topors protein is not detectable in several colon cancer cell lines. The human TOPORS gene is located on chromosome 9p21, with loss of heterozygosity in this region frequently observed in several different malignancies. While we were unable to detect loss of heterozygosity of the TOPORS gene in 16 sporadic colon cancer cases, increased methylation of a CpG island in the TOPORS promoter was evident in colon adenocarcinoma specimens relative to matched normal tissues. Additional studies indicate that forced expression of topors inhibits cellular proliferation and is associated with an accumulation of cells in the G0/G1 phase of the cell cycle. This effect is independent of the topors RING domain and maps to a C-terminal region of the protein. These results suggest that topors functions as a negative regulator of cell growth, and possibly as a tumor suppressor.

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Acknowledgements

This work was supported by Public Health Service Grants GM59170 and CA39662 from the National Cancer Institute. We thank Julie Friedman for assistance in obtaining human tissue specimens.

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Authors and Affiliations

  1. Department of Pharmacology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USA

    Ahamed Saleem, Jayeeta Dutta, Diptee Malegaonkar, Farheena Rasheed, Zeshaan Rasheed, Rajeev Rajendra, Henderson Marshall & Eric H Rubin

  2. Department of Molecular Genetics and Microbiology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USA

    Minje Luo & Honghua Li

  3. Department of Medicine, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USA

    Eric H Rubin

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  1. Ahamed Saleem
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Correspondence to Eric H Rubin.

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Saleem, A., Dutta, J., Malegaonkar, D. et al. The topoisomerase I- and p53-binding protein topors is differentially expressed in normal and malignant human tissues and may function as a tumor suppressor. Oncogene 23, 5293–5300 (2004). https://doi.org/10.1038/sj.onc.1207700

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