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.
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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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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DOI: https://doi.org/10.1038/sj.onc.1206689
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