Abstract
The cellular Brn-3a transcription factor is known to activate transcription of the genes encoding the human papilloma virus E6 and E7 proteins and is over-expressed in women with cervical neoplasia. We show that cervical cell lines with reduced Brn-3a expression show a greatly reduced ability to form tumours in nude mice compared to control cells and also show reduced expression of the HPV E6 and cellular Bcl-2 oncogenes. These effects are also observed in cervical cells over-expressing the related Brn-3b factor, which is known to antagonize activation of HPV gene expression by Brn-3a. These results demonstrate, for the first time, that inhibition of Brn-3a expression or enhanced Brn-3b expression can inhibit cervical cell-derived tumour growth in vivo as well as in vitro. Hence they establish Brn-3a as a key factor in cervical tumorigenesis and as a potential therapeutic target in human cervical neoplasia.
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References
Burghardt E . 1984 Clin. Obstet. Gynaecol. 11: 239–257
Cox MF, Meanwell CA, Maitland NJ, Blackledge G, Scully C, Jordan JA . 1986 Lancet 2: 157–158
Durst M, Gissmann L, Ikenberg H, Zur Hausen H . 1983 Proc. Natl. Acad. Sci. 80: 3812–3815
Gerrero MR, McEvilly RJ, Turner E, Lin CR, O'Connell S, Jenne KJ, Hobbs MV, Rosenfeld MG . 1993 Proc. Natl. Acad. Sci. USA 90: 10841–10845
Ho GYF, Bierman R, Beardsley L, Chang CJ, Burk RD . 1998 New Engl. J. Med. 338: 423–428
Lillycrop KA, Budhram-Mahadeo VS, Lakin ND, Terrenghi G, Wood JN, Polak JM, Latchman DS . 1992 Nucleic Acids Res. 20: 5093–5096
Meanwell CA . 1987 Lancet 1: 703–707
Morris PJ, Theil T, Ring CJA, Lillycrop KA, Möröy T, Latchman DS . 1994 Mol. Cell. Biol. 14: 6907–6914
Ndisang D, Budhram-Mahadeo V, Latchman DS . 1999 J. Biol. Chem. 274: 28521–28527
Ndisang D, Budhram-Mahadeo V, Singer A, Latchman DS . 2000 Clin. Sci. 98: 601–602
Ndisang D, Morris PJ, Chapman C, Ho L, Singer A, Latchman DS . 1998 J. Clin. Invest. 101: 1687–1692
Nobbenhuis MAE, Walboomers JMM, Helmerhorst TJM, Rozendaal L, Remmink AJ, Risse EKJ, van der Linden HC, Voorhorst FJ, Kenemans P, Meijer CJLM . 1999 Lancet 354: 20–25
Schiffman MH, Bauer HM, Hoover RN, Glass AG, Cadell DM, Rush BB, Scott DR, Sherman ME, Kurman RJ, Wacholder S . 1983 J. Natl. Cancer Inst. 85: 958–964
Smith MD, Dawson SJ, Boxer LM, Latchman DS . 1998a Nucleic Acids Res. 26: 4100–4107
Smith MD, Ensor EA, Coffin RS, Boxer LM, Latchman DS . 1998b J. Biol. Chem. 273: 16715–16722
Storey A, Thomas M, Kalita A, Harwood C, Gardiol D, Mantovani F, Breuer J, Leigh IM, Matlashewski G, Banks L . 1998 Nature 393: 229–234
van Duin M, Snijders PJF, Vossen MTM, Klaassen E, Voorhorst F, Verheijen RHM, Helmerhorst TJ, Meijer CJLM, Walboomers JMM . 2000 J. Gen. Virol. 81: 317–325
Verrijzer CP, van der Vliet PC . 1993 Biochimica. et Biophysica. Acta. 1173: 1–21
Acknowledgements
This work was supported by the Association for International Cancer Research (AICR) and WellBeing (Royal College of Obstetricians and Gynaecologists).
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Ndisang, D., Budhram-Mahadeo, V., Pedley, B. et al. The Brn-3a transcription factor plays a key role in regulating the growth of cervical cancer cells in vivo. Oncogene 20, 4899–4903 (2001). https://doi.org/10.1038/sj.onc.1204634
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DOI: https://doi.org/10.1038/sj.onc.1204634
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