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PHC3, a component of the hPRC-H complex, associates with 2A7E during G0 and is lost in osteosarcoma tumors

Oncogene volume 26, pages 1714–1722 (2007)Cite this article

Abstract

Polyhomeotic-like 3 (PHC3) is a ubiquitously expressed member of the polycomb gene family and part of the human polycomb complex hPRC-H. We found that in normal cells PHC3 associated with both hPRC-H complex components and with the transcription factor 2A7E. In differentiating and confluent cells, PHC3 and 2A7E showed nuclear colocalization in a punctate pattern that resembled the binding of polycomb bodies to heterochromatin. This punctate pattern was not seen in proliferating cells suggesting that PHC3 may be part of an 2A7E-polycomb complex that has been shown to occupy and silence target promoters in G0. Previous loss of heterozygosity (LoH) analyses had shown that the region containing PHC3 underwent frequent LoH in primary human osteosarcoma tumors. When we examined normal bone and human osteosarcoma tumors, we found loss of PHC3 expression in 36 of 56 osteosarcoma tumors. Sequence analysis revealed that PHC3 was mutated in nine of 15 primary osteosarcoma tumors. These findings suggest that loss of PHC3 may favor tumorigenesis by potentially disrupting the ability of cells to remain in G0.

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Acknowledgements

We thank Drs A Lichtler, Y-F Huang, D Pathmanathan, M Sciaudone and A Arnold for their helpful discussions and P Vachon, A Marren and V DuPaul-McGloin for their administrative support. We also thank the Childrens Oncology Group for their assistance. This work was supported by grants from the National Institutes of Health (CA074802 and AR049940), the Charlotte Geyer Foundation and the Murray-Heilig Foundation.

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Author notes

  1. A M Deshpande

    Present address: Molecular Oncology Research Institute, Tufts-New England Medical Center, Boston, MA, 02111, USA

Authors and Affiliations

  1. Center for Molecular Medicine, University of Connecticut Health Center, Farmington, CT, USA

    A M Deshpande, J D Akunowicz, B B Patel, E A Saria & M F Hansen

  2. Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA

    X T Reveles, S L Naylor & R J Leach

  3. Department of Pediatrics, The Children's Hospital at Montefiore, Bronx, NY, USA

    R G Gorlick

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  1. A M Deshpande
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Correspondence to M F Hansen.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Deshpande, A., Akunowicz, J., Reveles, X. et al. PHC3, a component of the hPRC-H complex, associates with 2A7E during G0 and is lost in osteosarcoma tumors. Oncogene 26, 1714–1722 (2007). https://doi.org/10.1038/sj.onc.1209988

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