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Multipotent PI-MECs are the true targets of MMTV-neu tumorigenesis

Oncogene volume 32, page 1338 (2013)Cite this article

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Lo et al.1 purport to identify the mammary tumor-inducing cells in mouse mammary tumor virus (MMTV)-neu transgenic mice to be derived from ‘luminal progenitors’. Despite some new experimental data that are mainly confirmatory, the authors do not discuss the fact that multiple research groups had previously reported the originating cells of MMTV-neu tumors. It is our collective opinion that none of the advances reported by the authors are unique to their experimental approach. Using genetically tagged cells in WAP-Cre/Rosa26-lox-STOP-lox-lacZ triple transgenic mice, Henry et al.2 reported that lacZ-positive parity-identified mammary epithelial cells (PI-MECs) were the targets for MMTV-neu tumorigenesis. In addition, PI-MECs were subsequently shown to be virtually 100% sorted into the CD49f-positive mammary epithelial fraction.3 Boulanger et al.4 showed that PI-MECs were multipotent and sensitive to tumor growth factor beta (TGFβ) expression, and Booth et al.5 showed that MMTV-neu induced mammary cancer cells (marked by lacZ expression) were suppressed by the normal mammary microenvironment but still maintained some of their multipotency. None of these reports were referenced or discussed by Lo et al.,1 although all of them are directly related to the experimental subject of this manuscript. These omissions are egregious and suggest at a minimum that the authors had not previewed the earlier literature relating to their studies. More importantly, the previous reports indicate that the targets for MMTV-neu are not ‘luminal progenitors’ but alveolar progenitors that are multipotent, express CD49f and are inhibited from expansion by both TGFβ expression and the absence of cyclin D1.6 These previously published works seriously diminish the scientific impact of the paper published by Lo et al.1 Further, in the light of these previous reports, the alleged novelty of the findings described in the article published by Lo et al. is misleading and a note of correction from Oncogene or these authors is appropriate.

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References

  1. Lo PK, Kanojia D, Liu X, Singh UP, Berger FG, Wang Q et al. CD49f and CD61 identify Her2/neu-induced mammary tumor-initiating cells that are potentially derived from luminal progenitors and maintained by the integrin-TGFβ signaling. Oncogene 2012; 31: 2614–2626.

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Authors and Affiliations

  1. University of Nebraska Medical Center, Omaha, NE, USA,

    K-U Wagner

  2. Clemson University, Clemson, NC, USA,

    B W Booth

  3. Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    C A Boulanger & G H Smith

Authors
  1. K-U Wagner
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  2. B W Booth
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  3. C A Boulanger
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  4. G H Smith
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Correspondence to G H Smith.

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Wagner, KU., Booth, B., Boulanger, C. et al. Multipotent PI-MECs are the true targets of MMTV-neu tumorigenesis. Oncogene 32, 1338 (2013). https://doi.org/10.1038/onc.2012.452

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