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BCL-6 is expressed in breast cancer and prevents mammary epithelial differentiation

Oncogene volume 22, pages 5572–5578 (2003)Cite this article

Abstract

Appropriately timed proliferation, differentiation and apoptosis are essential to the normal functions of the mammary epithelium. Here, we report that the transcription factor BCL-6 is expressed in mammary epithelium in nonpregnant animals as well as during early pregnancy. When overexpressed in the nontransformed EpH4 mammary epithelial cell line, BCL-6 prevents the STAT-driven expression of the milk protein β-casein and duct formation, and prevents apoptosis. Consistent with an antiapoptotic function, we demonstrate that BCL-6 is expressed in 68% of histologically high-grade ductal breast carcinomas, which are clinically the most aggressive. BCL-6 has previously been characterized as a regulator of B lymphocyte growth and development, but our work identifies a novel role for it in mammary epithelial differentiation, which may also implicate it in carcinogenesis.

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Abbreviations

EHS-ECM:

Engelbreth–Holm–Swarm-derived extra-cellular-matrix

ER:

oestrogen receptor

HGF/SF:

hepatocyte growth factor/scatter factor

STAT:

signal transducer and activator of transcription

References

  • Allman D, Jain A, Dent A, Maile R, Selvaggi T, Kehry M and Staudt L . (1996). Blood, 87, 5257–5268.

  • Bajalica-Lagerkrantz S, Piehl F, Farnebo F, Larsson C and Lagerkrantz J . (1998). Biochem. Biophys. Res. Commun., 247, 357–360.

  • Baron B, Anastasi J, Thirman M, Furukawa Y, Fears S, Kim D, Simone F, Birkenbach M, Montag A, Sadhu A, Zeleznik-Le N and McKeithan T . (2002). Proc. Natl. Acad. Sci. USA, 99, 2860–2865.

  • Bartkova J, Lukas J, Muller H, Lutzhoft D, Strauss M and Bartek J . (1994). Int. J. Cancer, 57, 353–361.

  • Boccaccio C, Ando M, Tamagnone L, Bardelli A, Michieli P, Battistini C and Comoglio P . (1998). Nature, 391, 285–288.

  • Buckley M, Sweeney K, Hamilton J, Sini R, Manning D, Nicholson R, deFazio A, Watts C, Musgrove E and Sutherland R . (1993). Oncogene, 8, 2127–2133.

  • Chang C, Ye B, Chaganti R and Dalla-Favera R . (1996). Proc. Natl. Acad. Sci. USA, 93, 6947–6952.

  • Dent A, Shaffer A, Yu X, Allman D and Staudt L . (1997). Science, 276, 589–592.

  • Desprez P-Y, Hara E, Bissell M and Campisi J . (1995). Mol. Cell. Biol., 15, 3398–3404.

  • Fukuda T, Yoshida T, Okada S, Hatano M, Miki T, Ishibashi K, Okabe S, Koseki H, Hirosawa S, Taniguchi M, Miyasaka N and Tokuhisa T . (1997). J. Exp. Med., 186, 439–448.

  • Harris M, Chang C-C, Berton M, Danial N, Zhang J, Kuehner D, Ye B, Kvatyuk M, Pandolfi P, Cattoretti G, Dalla-Favera R and Rothman P . (1999). Mol. Cell. Biol., 19, 7264–7275.

  • Kanazawa N, Moriyama M, Onizuka T, Sugawara K and Mori S . (1997). Pathol. Int., 47, 600–607.

  • Liu X, Robinson G and Hennighausen L . (1996). Mol. Endocrinol., 10, 1496–1506.

  • Mori S, Nishikawa S-I and Yokota Y . (2000). EMBO J., 19, 5772–5781.

  • Muschler J, Lochter A, Roskelly C, Yurchenco P and Bissell M . (1999). Mol. Biol. Cell, 10, 2817–2828.

  • Niemann C, Brinkmann V, Spitzer E, Hartmann G, Sachs M, Naundorf H and Birchmeier W . (1998). J. Cell. Biol., 143, 533–545.

  • Niu H, Ye B and Dalla-Favera R . (1998). Genes Dev., 12, 1953–1961.

  • Reljic R, Wagner S, Peakman L and Fearon D . (2000). J. Exp. Med., 192, 1841–1848.

  • Shaffer A, Yu X, He Y, Boldrick J, Chan E and Staudt L . (2000). Immunity, 13, 199–212.

  • Shvarts A, Brummelkamp T, Scheeren F, Koh E, Daley G, Spits H and Bernards R . (2002). Genes Dev., 16, 681–686.

  • Tang T, Dowbenko D, Jackson A, Toney L, Lewin D, Dent A and Lasky L . (2002). J. Biol. Chem., 277, 14255–14265.

  • Trusolino L, Bertotti A and Comiglio P . (2001). Cell, 107, 643–654.

  • van't Veer L, Dai H, van der Vijver M, He Y, Hart A, Mao M, Peterse H, van der Kooy K, Marton M, Witteveen A, Schreiber G, Kerkhoven R, Roberts C, Linsley P, Bernards R and Friend S . (2002). Nature, 415, 530–536.

  • Winklehner-Jennewein P, Geymayer S, Lechner J, Welte T, Hansson L, Geley S and Doppler W . (1998). Gene, 217, 127–139.

  • Ye B, Cattoretti G, Shen Q, Zhang J, Hawe N, Waard Rd, Leung C, Nouri-Shirazi M, Orazi A, Chaganti R, Rothman P, Stall A, Pandolfi P and Dalla-Favera R . (1997). Nat. Genet., 16, 161–170.

  • Ye B, Rao P, Chaganti R and Dalla-Favera R . (1993). Cancer Res., 53, 2732–2735.

  • Yoshida T, Fukuda T, Okabe S, Hatano M, Miki T, Hirosawa N, Miyasaka N, Isono K and Tokuhisa T . (1996). Biochem. Biophys. Res. Commun., 228, 216–220.

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Acknowledgements

This work was supported in part by a grant from the Wellcome Trust. SDW is the Royal Society Rink Research Fellow. We thank Professor Doug Fearon for a critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Medicine, Wellcome Trust Immunology Unit, University of Cambridge, Cambridge, CB2 2SP, UK

    Suresh Logarajah, Patricia Hunter, Matthew Kraman & Simon Wagner

  2. The Breakthrough Toby Robbins Breast Cancer Research Centre, Chester Beatty Laboratories, Fulham Road, London, SW3 6JB, UK

    Dawn Steele & Sunil Lakhani

  3. Department of Pathology, University of Cambridge, Cambridge, CB2 2XZ, UK

    Lynda Bobrow

  4. CR UK Department of Oncology & MRC Cancer Cell Unit, University of Cambridge, Cambridge, CB2 2XZ, UK

    Ashok Venkitaraman

  5. Department of Haematology, University of Cambridge, Cambridge, CB2 2XZ, UK

    Simon Wagner

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  1. Suresh Logarajah
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  2. Patricia Hunter
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Correspondence to Simon Wagner.

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Logarajah, S., Hunter, P., Kraman, M. et al. BCL-6 is expressed in breast cancer and prevents mammary epithelial differentiation. Oncogene 22, 5572–5578 (2003). https://doi.org/10.1038/sj.onc.1206689

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