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Molecular characterizations of Nop16 in murine mammary tumors with varying levels of c-Myc

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Abstract

NOP16, also known as HSPC111, has been identified as a MYC and estrogen regulated gene in in vitro studies, hence coexpression levels were strongly correlated. Importantly, high expression of NOP16 was associated with poor clinical outcome in breast cancer patients. However, coexpression of NOP16, MYC and estrogen receptor (ESR1) varied widely in tumors and cell lines suggesting that transcriptional regulation differed according to pathological environments. The goal of this study was to determine the expression patterns of Nop16, Myc and Esr1 in murine mammary tumors with disparate histopathological and molecular features. We hypothesized that tumor environments with relatively high Myc levels would have different coexpression patterns than tumor environments with relatively low Myc levels. We measured levels of Myc and Nop16 mRNA and protein in tumors from WAP-c-myc mice that were of high grade and metastasized frequently. In contrast, Myc and Nop16 mRNA and proteins levels were significantly lower in the less aggressive tumors that developed in NRL-TGFα mice. Tumors from both mouse lines express ESR1 protein and we found that Esr1 mRNA levels correlated positively with Myc levels in both models. However, Myc and Nop16 transcript levels correlated positively only in tumors from NRL-TGFα mice. We identified prominent NOP16 protein in nuclei and less prominent staining in the cytoplasm of luminal cells of ducts and lobules from normal mammary glands as well as in hyperplasias and tumors obtained from NRL-TGFα mice. This staining pattern was reversed in tumors from WAP-c-Myc mice as nuclear staining was faint or absent and cytoplasmic staining more pronounced. In summary, the regulation of expression and localization of NOP16 varies in tumor environments with high versus low MYC levels and demonstrate the importance of stratifying clinical breast cancers based on MYC levels.

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Acknowledgments

The authors greatly appreciate the assistance of Barbara Elmquist and Emily Heid for excellent preparation of tissues for histologic and immunohistochemical review and Drs. Jon Holy and Lois Heller for critical review of this manuscript. This work was supported by NIH grant K01-RR00145, the University of Minnesota Medical Foundation the Academic Health Center to TRH, the University of Minnesota Undergraduate Research Opportunities Program to ES and by St. Luke’s Hospital-Duluth.

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Authors and Affiliations

  1. Department of Pathology, University of Minnesota Medical School-Duluth Campus, 1035 University Drive, Duluth, MN, 55812, USA

    Donald W. Kundel

  2. Department of Physiology and Pharmacology, University of Minnesota Medical School-Duluth Campus, 1035 University Drive, Duluth, MN, 55812, USA

    Emily Stromquist, Olga Zhdankin & Teresa A. Rose-Hellekant

  3. Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, 31404, USA

    Amy L. Greene

  4. Department of Mathematics and Statistics, University of Minnesota Duluth, 1035 University Drive, Duluth, MN, 55812, USA

    Ronald R. Regal

Authors
  1. Donald W. Kundel
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  2. Emily Stromquist
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  3. Amy L. Greene
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  4. Olga Zhdankin
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  5. Ronald R. Regal
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  6. Teresa A. Rose-Hellekant
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Corresponding author

Correspondence to Teresa A. Rose-Hellekant.

Electronic supplementary material

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Online Resource 1

NOP16, located on human chromosome 5, is found in a region syntenic to mouse chromosome 13. The human and mouse DNA and proteins share 84.4 and 91% identity, respectively. The syntenic alignment of mouse and human NOP16 was performed using Ensembl release 56, September 2009 (Hubbard et al. 2009). The human mir-1271 located in the NOP16 region of synteny is untested as a regulatory miRNA but expression was recently demonstrated in teratomas (Nygaard et al. 2009), embryonic stem cells and embryoid bodies (Morin et al. 2008) by deep-sequencing. The homolog in mouse, the ncRNA gene AC155262.2, has not as yet been investigated (PDF 18313 kb)

Online Resource 2

Selection of antibodies for identification of NOP16 in mouse tissues. Antibodies directed against human NOP16 protein, a mouse polyclonal antibody (#88449 from Abcam) and a rabbit polyclonal antibody (H00051491-D01 from Abnova) were tested in protein extracts from mouse spleen. Both primary antibodies identified proteins of the same size expected for NOP16, however the anti-mouse HRP conjugated secondary antibody produced a non-specific secondary band denoted as “background band”. Note also that incubation of lysates with rabbit polyclonal antibody resulted in bands with higher signal than lysate incubated with mouse monoclonal antibody (TIFF 3282 kb)

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Kundel, D.W., Stromquist, E., Greene, A.L. et al. Molecular characterizations of Nop16 in murine mammary tumors with varying levels of c-Myc . Transgenic Res 21, 393–406 (2012). https://doi.org/10.1007/s11248-011-9529-3

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  • DOI: https://doi.org/10.1007/s11248-011-9529-3

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