1. Oncogenic human papillomaviruses block expression of theB‐cell translocation gene‐2tumor suppressor gene
- Author
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Felix Hoppe-Seyler, Claudia Lohrey, Matthias Dürst, Martin Scheffner, Susanne Dymalla, Claire Cullmann, and Karin Hoppe-Seyler
- Subjects
Cancer Research ,Tumor suppressor gene ,Viral Oncogene ,Biology ,medicine.disease_cause ,Immediate-Early Proteins ,ddc:570 ,medicine ,Humans ,Gene silencing ,Genes, Tumor Suppressor ,Cell Proliferation ,Human papillomavirus 16 ,Humanes Papillomavirus [gnd] ,BTG2 ,Human papillomavirus 18 ,Oncogene ,Tumor Suppressor Proteins ,Oncogene Proteins, Viral ,Molecular biology ,DNA-Binding Proteins ,Repressor Proteins ,Oncology ,Cancer cell ,Cancer research ,Ectopic expression ,Tumor Suppressor Protein p53 ,Carcinogenesis ,HeLa Cells - Abstract
Human papillomavirus (HPV)-induced carcinogenesis is critically dependent on the activities of the viral E6 and E7 oncogenes. Here, we demonstrate that expression of the putative tumor suppressor gene B-cell translocation gene-2 (BTG2) is reinduced in HPV16- and HPV18-positive cancer cells on silencing of viral oncogene expression, indicating that BTG2 is repressed by oncogenic HPVs. Inhibition of BTG2 expression was mediated by the HPV E6 oncogene and occurred in a p53-dependent manner. Luciferase reporter gene analyses revealed that BTG2 repression takes place at the transcriptional level and is dependent on the integrity of the major p53-response element within the BTG2 promoter. Ectopic expression of BTG2 acted antiproliferative in cervical cancer cells. Tissue specimens commonly exhibited reduced BTG2 protein levels in HPV-positive high-grade lesions (CIN2/3) and cervical carcinomas, when compared with normal cervical epithelium. These findings identify the antiproliferative BTG2 gene as a novel cellular target blocked by the HPV E6 oncoprotein. © 2009 UICC
- Published
- 2009