The HPV-activating cellular transcription factor Brn-3a is overexpressed in CIN3 cervical lesions.

Abstract

The cervical cellular transcription factors Brn-3a and Brn-3b have antagonistic effects on transcription of the human papilloma virus types 16 and 18 E6 and E7 oncogenes, with Brn-3a activating expression and Brn-3b repressing it. We therefore measured expression of Brn-3a and Brn-3b mRNAs in biopsies from 16 women with no detectable cervical abnormality, and in 14 women with cervical intraepithelial neoplasia grade 3 (CIN3) lesions. Although the mean level of Brn-3b expression was similar in both groups, the mean level of Brn-3a expression was over 300-fold higher in the CIN3 samples when compared with normals. Elevated expression of Brn-3a was also detected in 16 histologically normal regions of the cervix adjacent to the CIN3 lesions, indicating that elevation of Brn-3a levels is not confined to the lesion in women with CIN3, and is thus not a consequence of the oncogenic process.

The Brn-3b POU family transcription factor represses expression of the BRCA-1 anti-oncogene in breast cancer cells

“…To quantitate the level of Brn-3a and Brn-3b mRNAs we used a reverse transcriptase/polymerase chain reaction (RT ± PCR) assay which we have previously used to reliably quantitate these mRNAs in small amounts of clinical and other material (Ndisang et al, 1998;Smith and Latchman, 1996). This assay was used to compare the levels of Brn-3a and Brn-3b mRNAs in normal breast tissue or benign breast tumour material with that obtained from malignant breast tumours from pre-or post-menopausal women.…”

“…Membranes were exposed to ®lms, (Eastman Kodak Co., Rochester, NY, USA) and the subsequent autoradiographs were then analysed using a densitometer (Bio-Rad Laboratories, Hercules, CA, USA). We have previously shown that this blotting procedure, in conjunction with the RT ± PCR conditions used, allows accurate quanti®cation of the Brn-3a and Brn-3b mRNAs relative to the constitutively expressed cyclophilin mRNA (Lillycrop et al, 1992;Ndisang et al, 1998;Morris et al, 1994).…”

“…Brn-3a, Brn-3b and Brn-3c are closely related members of the POU family which are encoded by di erent genes (Theil et al, 1993) and are expressed in distinct but overlapping patterns in the developing and adult nervous system (He et al, 1989;Gerrero et al, 1993;Lillycrop et al, 1992;Turner et al, 1994;Ninkina et al, 1993). In addition however, expression of Brn-3a and Brn-3b has also been detected in some non neuronal cells such as cervical epithelium (Lillycrop et al, 1992;Ndisang et al, 1998) and in the testis (Budhram-Mahadeo et al, submitted).…”

“…In addition however, expression of Brn-3a and Brn-3b has also been detected in some non neuronal cells such as cervical epithelium (Lillycrop et al, 1992;Ndisang et al, 1998) and in the testis (Budhram-Mahadeo et al, submitted).…”

“…Moreover, we have recently shown that mean Brn-3a levels are increased over 300-fold in human samples exhibiting cervical intra-epithelial neoplasia grade 3 (CIN3) compared to normal human cervical samples whereas Brn-3b levels are similar in the two groups of samples (Ndisang et al, 1998). Such a ®nding is of particular interest in view of the ability of Brn-3a to activate the human papilloma virus type 16 and type 18 promoter whereas Brn-3b represses this promoter (Morris et al, 1994).…”