The Brn-3a transcription factor plays a key role in regulating the growth of cervical cancer cells in vivo

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 hues 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.