Ndisang D, Budhram-Mahadeo V, Pedley B, Latchman D S
Medical Molecular Biology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
Oncogene. 2001 Aug 9;20(35):4899-903. doi: 10.1038/sj.onc.1204634.
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.
已知细胞Brn-3a转录因子可激活编码人乳头瘤病毒E6和E7蛋白的基因转录，且在宫颈肿瘤形成的女性中过度表达。我们发现，与对照细胞相比，Brn-3a表达降低的宫颈细胞系在裸鼠中形成肿瘤的能力大大降低，同时HPV E6和细胞Bcl-2癌基因的表达也降低。在过表达相关Brn-3b因子的宫颈细胞中也观察到了这些效应，已知Brn-3b因子可拮抗Brn-3a对HPV基因表达的激活作用。这些结果首次证明，抑制Brn-3a表达或增强Brn-3b表达可在体内和体外抑制宫颈细胞衍生的肿瘤生长。因此，它们确立了Brn-3a作为宫颈肿瘤发生的关键因素以及人类宫颈肿瘤潜在治疗靶点的地位。
