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WISP3 is a novel tumor suppressor gene of inflammatory breast cancer

Oncogene volume 21, pages 3172–3180 (2002)Cite this article

Abstract

Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a 5-year disease-free survival of less than 45%. Little is known about the genetic alterations that result in IBC. In our previous work, we found that WISP3 was specifically lost in human IBC tumors when compared to stage-matched, non-IBC tumors. We hypothesize that WISP3 has tumor suppressor function in the breast and that it may be a key genetic alteration that contributes to the unique IBC phenotype. The full-length WISP3 cDNA was sequenced and cloned into an expression vector. The resulting construct was introduced in to the SUM149 cell line that was derived from a patient with IBC and lacks WISP3 expression. In soft agar, stable WISP3 transfectants formed significantly fewer colonies than the controls. Stable WISP3 transfectants lost their ability to invade and had reduced angiogenic potential. WISP3 transfection was effective in suppressing in vivo tumor growth in nude mice. Mice bearing WISP3 expressing tumors had a significantly longer survival than those with vector-control transfectant tumors. Our data demonstrate that WISP3 acts as a tumor suppressor gene in the breast. Loss of WISP3 expression contributes to the phenotype of IBC by regulating tumor cell growth, invasion and angiogenesis.

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Acknowledgements

We thank Wendy Kutz and Matthew Warman from Case Western Reserve University for providing anti-WISP3 polyclonal antibody. We thank Satoru Hayasaka for statistical support, and Elizabeth Horn and Robin Kunkel for artwork. Work supported in part by DOD grant DAMD17-00-1-0636 (CG Kleer), and NIH grants RO1CA77612 (SD Merajver), P30CA46592, M01-RR00042 and DAMD17-00-0345 (SD Merajver).

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Authors and Affiliations

  1. Department of Pathology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA

    Celina G Kleer & Yanhong Zhang

  2. Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA

    Quintin Pan, Kenneth L van Golen, Zhi-Fen Wu & Sofia D Merajver

  3. Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA

    D Livant

Authors
  1. Celina G Kleer
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  2. Yanhong Zhang
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  3. Quintin Pan
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  4. Kenneth L van Golen
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  5. Zhi-Fen Wu
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  6. D Livant
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  7. Sofia D Merajver
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Correspondence to Celina G Kleer.

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Kleer, C., Zhang, Y., Pan, Q. et al. WISP3 is a novel tumor suppressor gene of inflammatory breast cancer. Oncogene 21, 3172–3180 (2002). https://doi.org/10.1038/sj.onc.1205462

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