Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Downregulation of Muc1 in MMTV-c-Neu tumors

Oncogene volume 23, pages 697–705 (2004)Cite this article

Abstract

MUC1 is a tumor antigen, overexpressed in approximately 90% of human breast cancers. In normal glandular epithelia, MUC1 is expressed at the apical surface; however, in carcinomas an aberrantly glycosylated form of MUC1 is upregulated and expressed around the entire surface of the cell. Previously, we have shown that a lack of Muc1 significantly delays tumor progression and/or onset in MMTV-PyV-mT and MMTV-Wnt-1 transgenic mice. Here we show that, unlike the models mentioned above, a loss of Muc1 in MMTV-c-Neu mice (MMTV-c-Neu/Muc1−/−) altered neither mammary tumor onset nor progression. Moreover, characterization of MMTV-c-Neu/Muc1+/+ tumors revealed that Muc1 expression was repressed at the level of transcription. In contrast, normal mammary gland tissue adjacent to tumor tissue expressed Muc1 and pregnant mammary glands from c-Neu transgenic animals expressed high levels of Muc1. We found that transient transfection of activated ErbB2 into human embryonic kidney 293/MUC1 cells resulted in the repression of MUC1 expression. Further, transient transfection of activated ErbB2 resulted in the inhibition of Muc1 transcriptional activation in luciferase reporter assays. These data suggest that the activation of ErbB2, which only occurs in c-Neu tumors, selectively inhibits Muc1 expression.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Akewanlop C, Watanabe M, Singh B, Walker M, Kufe DW and Hayes DF . (2001). Cancer Res., 61, 4061–4065.

  • Bloom H and Richardson W . (1957). Br. J. Cancer, 11, 359–377.

  • Croce MV, Isla-Larrain MT, Rua CE, Rabassa ME, Gendler SJ and Segal-Eiras A . (2003). J. Histochem. Cytochem., 51, 781–788.

  • Engelman JA, Lee RJ, Karnezis A, Bearss DJ, Webster M, Siegel P, Muller WJ, Windle JJ, Pestell RG and Lisanti MP . (1998). J. Biol. Chem., 273, 20448–20455.

  • Guaita S, Puig I, Franci C, Garrido M, Dominguez D, Batlle E, Sancho E, Dedhar S, De Herreros AG and Baulida J . (2002). J. Biol. Chem., 277, 39209–39216.

  • Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD and Muller WJ . (1992). Proc. Natl. Acad. Sci. USA, 89, 10578–10582.

  • Hilkens J, Buijs F, Hilgers J, Hageman P, Calafat J, Sonnenberg A and van der Valk M . (1984). Int. J. Cancer, 34, 197–206.

  • Khoury H, Dankort DL, Sadekova S, Naujokas MA, Muller WJ and Park M . (2001). Oncogene, 20, 788–799.

  • Kwong KY and Hung MC . (1998). Mol. Carcinog., 23, 62–68.

  • Larsen A and Weintraub H . (1982). Cell, 29, 609–622.

  • McGuckin MA, Walsh MD, Hohn BG, Ward BG and Wright RG . (1995). Hum. Pathol., 26, 432–439.

  • Mirkin SM, Lyamichev VI, Drushlyak KN, Dobrynin VN, Filippov SA and Frank-Kamenetskii MD . (1987). Nature, 330, 495–497.

  • Nelson KL, Becker NA, Pahwa GS, Hollingsworth MA and Maher III LJ . (1996). J. Biol. Chem., 271, 18061–18067.

  • Peat N, Gendler SJ, Lalani N, Duhig T and Taylor-Papadimitriou J . (1992). Cancer Res., 52, 1954–1960.

  • Revillion F, Bonneterre J and Peyrat JP . (1998). Eur. J. Cancer, 34, 791–808.

  • Rochlitz CF, Scott GK, Dodson JM, Liu E, Dollbaum C, Smith HS and Benz CC . (1989). Cancer Res., 49, 357–360.

  • Rowse GJ, Ritland SR and Gendler SJ . (1998b). Cancer Res., 58, 2675–2679.

  • Rowse GJ, Tempero RM, VanLith ML, Hollingsworth MA and Gendler SJ . (1998a). Cancer Res., 58, 315–321.

  • Schroeder JA, Adriance MC, Thompson MC, Camenisch TD and Gendler SJ . (2003). Oncogene, 22, 1324–1332.

  • Schroeder JA, Thompson MC, Gardner MM and Gendler SJ . (2001). J. Biol. Chem., 276, 13057–13064.

  • Scibetta AG, Albanese I, Morris J, Cooper L, Downward J, Rowe P and Taylor-Papadimitriou J . (2001). DNA Cell Biol., 20, 265–274.

  • Shiraga T, Smith D, Nuthall HN, Hollingsworth MA and Harris A . (2002). Mol. Med., 8, 33–41.

  • Siegel PM, Dankort DL, Hardy WR and Muller WJ . (1994). Mol. Cell. Biol., 14, 7068–7077.

  • Siegel PM and Muller WJ . (1996). Proc. Natl. Acad. Sci. USA, 93, 8878–8883.

  • Siegel PM, Ryan ED, Cardiff RD and Muller WJ . (1999). EMBO J., 18, 2149–2164.

  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A and McGuire WL . (1987). Science, 235, 177–182.

  • Spicer AP, Parry G, Patton S and Gendler SJ . (1991). J. Biol. Chem., 266, 15099–15109.

  • Spicer AP, Rowse GJ, Lidner TK and Gendler SJ . (1995). J. Biol. Chem., 270, 30093–30101.

  • Turner BC, Zhang J, Gumbs AA, Maher MG, Kaplan L, Carter D, Glazer PM, Hurst HC, Haffty BG and Williams T . (1998). Cancer Res., 58, 5466–5472.

  • Witton CJ, Reeves JR, Going JJ, Cooke TG and Bartlett JM . (2003). J. Pathol., 200, 290–297.

  • Xing PX, Tjandra JJ, Stacker SA, Teh JG, Thompson CH, McLaughlin PJ and McKenzie IF . (1989). Immunol. Cell Biol., 67 (Part 3), 183–195.

  • Zotter S, Hageman PC, Lossnitzer A, Mooi WJ and Hilgers J . (1988). Cancer Rev., 11–12, 55–101.

Download references

Acknowledgements

We thank Christopher J Sterner for excellent technical assistance in the breeding and palpation of the c-Neu/Muc1+/+ and c-Neu/Muc1−/− mice. We also thank Dr Yosef Yarden and Dr Nancy Hynes for ErbB2 constructs, Dr Yaacov Barak for Muc1 deletion constructs, Dr William Muller for the c-Neu transgenic mice, Dr David Lee for the c-Neu probe, Dr Robert Oshima for the keratin 18 cDNA probe, Jim Tarara and Linda Murphy for technical support, and Dr Patrick Roche for providing human breast tumor sections. We also thank Suresh Savarirayan, and animal care attendants for animal care, Marvin Ruona for computer graphics, and Carol Williams for manuscript preparation and submission. This work was supported by NIH CA064389 (SJG), NIH predoctoral fellowship CA090205 (MCA), and the Mayo Foundation.

Author information

Author notes

  1. Melissa C Adriance

    Present address: Lawrence Berkeley National Lab, Cell and Molecular Biology, 1 Cyclotron Road, MS 83-101, Berkeley, CA, 94720, USA

Authors and Affiliations

  1. Tumor Biology Program, Mayo Medical/Graduate School, Mayo Clinic Scottsdale, Scottsdale, 85259, AZ, USA

    Melissa C Adriance & Sandra J Gendler

  2. Department of Biochemistry and Molecular Biology, Mayo Medical/Graduate School, Mayo Clinic Scottsdale, Scottsdale, 85259, AZ, USA

    Sandra J Gendler

Authors
  1. Melissa C Adriance
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandra J Gendler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sandra J Gendler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adriance, M., Gendler, S. Downregulation of Muc1 in MMTV-c-Neu tumors. Oncogene 23, 697–705 (2004). https://doi.org/10.1038/sj.onc.1207165

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207165

Keywords

This article is cited by

Search

Advanced search

Quick links