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Ets2-dependent microenvironmental support of mouse mammary tumors

Oncogene volume 24, pages 6870–6876 (2005)Cite this article

Abstract

Decreasing the amount of active mouse Ets2 transcription factor by half in mice or use of a MAP kinase insensitive hypomorphic targeted Ets2 allele restricts the appearance of transgenic mammary tumors caused by either Polyoma middle T antigen (PyMT) or activated Neu/ErbB2. In addition, the early growth of transplanted mammary tumors is limited by restricted Ets2 activity of the host. Here we have tested genetically, with the use of a conditional Ets2flox allele and tissue specific Cre recombinase expression, whether Ets2 also functions within tumor cells by inactivating Ets2 within mammary luminal epithelial cells from which transgenic PyMTY315/322F tumors arise. We find that inactivation of Ets2 within tumor cells has no effect on tumor appearance or growth. By contrast, complete inactivation of Ets2 in both epithelial and stromal cells moderates the early hyperplastic phase of tumor development and the time of tumor appearance but does not prevent tumor occurrence and has no detectable effect on tumor growth. Thus, Ets2 supports mammary tumors exclusively through their microenvironment.

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Acknowledgements

We thank Dr Craig Hauser for helpful discussions and the Burnham Institute Animal Facility personnel for careful animal husbandry. This work was supported by grants from National Cancer Institute (CA74547 and CA098778 to RGO), the Department of Defense BCRP Predoctoral Fellowship (DAMD17-02-1-0316 to FW), and the National Cancer Institute Training Grant (1T32CA77109-04 to JAT).

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Author notes

  1. John A Tynan and Fang Wen: These authors contributed equally to this work

Authors and Affiliations

  1. Graduate Program in Molecular Pathology, University of California, San Diego, 9500 Gilman Drive 0612, La Jolla, 92093, CA, USA

    John A Tynan, Fang Wen & Robert G Oshima

  2. Molecular Oncology Group, McGill University, 687, Pine Avenue West, Room H5.63A, Montreal, PQ H3A 1A1, Canada

    William J Muller

  3. Oncodevelopmental Biology Program, Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, 92037, CA, USA

    John A Tynan, Fang Wen & Robert G Oshima

Authors
  1. John A Tynan
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  2. Fang Wen
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  4. Robert G Oshima
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Correspondence to Robert G Oshima.

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Tynan, J., Wen, F., Muller, W. et al. Ets2-dependent microenvironmental support of mouse mammary tumors. Oncogene 24, 6870–6876 (2005). https://doi.org/10.1038/sj.onc.1208856

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