Abstract
We have previously demonstrated decreased Jun/AP-1 activity in the breast cancer cell line MCF-7 when compared to normal or immortalized mammary epithelial cells. In this paper, we overexpress Jun in MCF-7 cells (MCF7Jun) and demonstrate that it results in diverse biologic and biochemical changes, which mimic those seen clinically in breast cancer. Overexpression of Jun causes significant alterations in the composition of AP-1, decreased junB and increased fra-1 expression and results in an increased biologic aggressiveness. MCF7Jun cells exhibit increased cellular motility, increased expression of a matrix degrading enzyme MMP-9, increased in vitro chemoinvasion and tumor formation in nude mice in the absence of exogenous estrogens. Furthermore, MCF7Jun cells are unresponsive to the growth stimulating effects of estrogen and growth inhibitory effects of tamoxifen. Analysis of the estrogen receptor (ER) expression and activity showed that the MCF7Jun cells have no detectable ER. MCF-7 cells overexpressing mutant forms of cJun were responsive to the growth stimulatory effects of estrogen indicating that full-length cJun is required to acquire the estrogen-independent phenotype in breast cancer cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Alani R, Brown P, Binetruy B, Dosaka H, Rosenberg R, Angel P and Karin M. . 1991 Mol. Cell. Biol. 11: 6286–6295.
Angel P, Allegretto EA, Okino ST, Hattori K, Boyle WJ, Hunter T and Karin M. . 1988 Nature 332: 166–171.
Angel P, Imagawa M, Chiu RJ, Stein B, Inmbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P and Karin M. . 1987 Cell 49: 729–739.
Angel P and Karin M. . 1991 Biochim. Biophys. Acta 1072: 129–157.
Bignon E, Pons M, Crastes de Paulet A, Dore JC, Gilbert J, Miquel JF, Pons M and Raynaud JP. . 1989 J. Med. Chem. 32: 2092–2103.
Bohmann D, Bos TJ, Admon A, Nishimura T, Vogt PK and Tjian R. . 1987 Science 238: 1386–1392.
Brown PH, Kim SH, Wise SC, Sabichi AL and Birrer MJ. . 1996 Cell Growth Differ. 7: 1013–1021.
Castellazzi M, Dangy J-P, Mechta F, Hirai S-I, Yaniv M, Samarut J, Lassailly A and Brun G. . 1990 Oncogene 5: 1541–1547.
Chen TK, Smith LM, Gebhardt DK, Birrer MJ and Brown PH. . 1996 Mol. Carcinogen. 15: 215–226.
Clarke R, Brunner N, Katzenellenbogen BS, Thompson EW, Norman MJ, Koppi C, Paik S, Lippman ME and Dickson RB. . 1989 Proc. Natl. Acad. Sci. USA 86: 3649–3653.
Clarke R, Brunner N, Thompson EW, Glanz P, Katz D, Dickson RB and Lippman ME. . 1989 J. Endocrinol. 122: 331–340.
Clarke R, Dickson RB and Brunner N. . 1990 Ann. Oncol. 1: 401–407.
Darbon J, Valette A and Bayard F. . 1986 Biochem. Pharmacol. 35 (16): 2683–2686.
Deng T and Karin M. . 1993 Genes Dev. 7: 479–490.
Dickson R. . 1995 Molecular Biology in Cancer Medicine. R Kurzrock and M Talpaz (eds).. Martin Dunitz Ltd: London pp. 241–272.
Domann FE, Levy JP, Birrer MJ and Bowden GT. . 1994 Cell Growth Differ. 5: 9–16.
Dong Z, Birrer MJ, Watts RG, Matrisian LM and Colburn NH. . 1994 Proc. Natl. Acad. Sci. USA 91: 609–613.
Doucas V, Spyrou G and Yaniv M. . 1991 EMBO J. 10 (8): 2237–2245.
Dumont JA, Bitonti AJ, Wallace CD, Baumann RJ, Cashman EA and Cross-Doersen DE. . 1996 Cell Growth Differ. 7: 351–359.
Fialka I, Scharwz H, Reichmann E, Oft M, Busslinger M and Beug H. . 1996 J. Cell Biol. 132: 1115–1132.
Holst-Hansen C, Johannessen B, Hoyer-Hansen G, Romer J, Ellis V and Brunner N. . 1996 Clin. Exp. Metastasis 14: 297–307.
Jain J, McCaffrey PG, Miner Z, Kerppola TK, Lambert J, Verdine GL, Curran T and Rao A. . 1993 Nature 365: 352–355.
Johnston SR, Lu B, Scott GK, Kushner PJ, Dowsett M and Benz CC. . 1999 Clin. Cancer Res. 5: 251–256.
Lambert PA, Somers KD, Kohn EC and Perry RR. . 1997 Surgery 122: 372–379.
Leonessa F, Boulay V, Wright A, Thompson EW, Brunner N and Clarke R. . 1991 Acta Oncol. 31: 115–123.
McPherson LA, Baichwal VR and Weigel RJ. . 1997 Proc. Natl. Acad. Sci. USA 94: 4342–4347.
Ritke MK, Bergoltz VV, Allan WP and Yalowich JC. . 1994 Biochem. Pharmacol. 48: 525–533.
Saceda M, Knabbe C, Dickson RB, Lipmann ME, Bronzert D, Lindsey RK, Gottardis MM and Martin MB. . 1991 J. Biol. Chem. 266: 17809–17814.
Sato H and Seiki M. . 1993 Oncogene 8: 395–405.
Schutte J, Minna JD and Birrer MJ. . 1989 Proc. Natl. Acad. Sci. USA 86: 2257–2261.
Smith LM, Birrer MJ, Stampfer MR and Brown PH. . 1997 Cancer Res. 57: 3046–3054.
Stanier RY, Adelberg EA and Ingraham JL. . 1976 The Microbial World. Prentice Hall, Inc.: New Jersey pp. 276–277.
Stein B, Baldwin Jr AS, Ballard DW, Greene WC, Angel P and Herrlich P. . 1993 EMBO J. 12 (10): 3879–3891.
Suzuki T, Hashimoto Y, Sato H, Nishina H and Iba H. . 1991 Jpn. J. Cancer Res. 82: 58–64.
Szabo E, Riffe ME, Steinberg SM, Birrer MJ and Linnoila RI. . 1996 Cancer Res. 56: 305–315.
Tang Z, Treilleux I and Brown M. . 1997 Mol. Cell. Biol. 17 (3): 1274–1280.
Tzukerman M, Zhang X-K and Pfahl M. . 1991 Mol. Endocrinol. 91: 1983–1992.
Thompson EW, Brunner N, Torri J, Johnson MD, Boulay V, Wright A, Lippman ME, Steeg PS and Clarke R. . 1993 Clin. Exp. Metastasis 11: 15–26.
Uht RM, Anderson CM, Webb P and Kushner PJ. . 1997 Endocrinol. 138 (7): 2900–2908.
Vig E, Barrett TJ and Vedeckis V. . 1994 Mol. Endocrinol. 8: 1336–1346.
Vogt PK and Bos TJ. . 1990 Adv. Cancer Res. 55: 1–35.
Yang L, Kim H, Munoz-Medellin D, Reddy P and Brown PH. . 1997 Cancer Res. 57: 4652–4661.
Yang-Yen HF, Chambard JC, Sun YL, Smeal T, Schmidt TJ, Drouin J and Karin M. . 1990 Cell 62: 1205–1215.
Yoshioka K, Deng T, Cavigelli M and Karin M. . 1995 Proc. Natl. Acad. Sci. USA 92: 4972–4976.
Acknowledgements
LM Smith and SC Wise are co-first authors for this study. We thank Dr M Karin and Dr P Chambon for their generous gifts of plasmids. We also thank Amy Guzzone for her technical expertise.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Smith, L., Wise, S., Hendricks, D. et al. cJun overexpression in MCF-7 breast cancer cells produces a tumorigenic, invasive and hormone resistant phenotype. Oncogene 18, 6063–6070 (1999). https://doi.org/10.1038/sj.onc.1202989
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1202989
Keywords
This article is cited by
-
The E3 ligase COP1 promotes ERα signaling and suppresses EMT in breast cancer
Oncogene (2022)
-
Selective antagonism of cJun for cancer therapy
Journal of Experimental & Clinical Cancer Research (2020)
-
PGK1 facilities cisplatin chemoresistance by triggering HSP90/ERK pathway mediated DNA repair and methylation in endometrial endometrioid adenocarcinoma
Molecular Medicine (2019)
-
Dynamic interactions between the extracellular matrix and estrogen activity in progression of ER+ breast cancer
Oncogene (2019)
-
miR-29a contributes to breast cancer cells epithelial–mesenchymal transition, migration, and invasion via down-regulating histone H4K20 trimethylation through directly targeting SUV420H2
Cell Death & Disease (2019)