Retinoic acid-mediated repression of human papillomavirus 18 transcription and different ligand regulation of the retinoic acid receptor beta gene in non-tumorigenic and tumorigenic HeLa hybrid cells.

摘要: Human papillomavirus type 18 (HPV18) belongs to the group of genital papillomaviruses involved in development cervical carcinomas. Since retinoic acid (RA) is a key regulator epithelial cell differentiation and growth inhibitor vitro HPV18-positive HeLa carcinoma cells, we have used hybrid cells order analyse effects RA on expression HPV18 E6 E7 oncogenes cellular receptor genes RAR-beta -gamma. We show here that down-regulates mRNA levels apparently due transcriptional repression. Transient cotransfection assays indicated RARs negatively regulate upstream regulatory region central enhancer can confer RA-dependent repression heterologous promoter. treatment resulted induction non-tumorigenic but not tumorigenic segregants nor cells. No alterations gene or promoter could be revealed by Southern DNA sequence analysis, respectively. As determined transient transfection assays, however, control was activated more strongly than thus indicating differences trans-acting factors. Our data suggest are potential negative regulators expression, dysregulation either causatively contributes an indicator tumorigenicity