Oncogenic human papillomaviruses block expression of the B-cell translocation gene-2 tumor suppressor gene

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2009
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Cullmann, Claire
Hoppe-Seyler, Karin
Dymalla, Susanne
Lohrey, Claudia
Dürst, Matthias
Hoppe-Seyler, Felix
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International Journal of Cancer. 2009, 125(9), pp. 2014-2020. ISSN 0020-7136. eISSN 1097-0215. Available under: doi: 10.1002/ijc.24671
Zusammenfassung

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.

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570 Biowissenschaften, Biologie
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ISO 690CULLMANN, Claire, Karin HOPPE-SEYLER, Susanne DYMALLA, Claudia LOHREY, Martin SCHEFFNER, Matthias DÜRST, Felix HOPPE-SEYLER, 2009. Oncogenic human papillomaviruses block expression of the B-cell translocation gene-2 tumor suppressor gene. In: International Journal of Cancer. 2009, 125(9), pp. 2014-2020. ISSN 0020-7136. eISSN 1097-0215. Available under: doi: 10.1002/ijc.24671
BibTex
@article{Cullmann2009Oncog-1250,
  year={2009},
  doi={10.1002/ijc.24671},
  title={Oncogenic human papillomaviruses block expression of the B-cell translocation gene-2 tumor suppressor gene},
  number={9},
  volume={125},
  issn={0020-7136},
  journal={International Journal of Cancer},
  pages={2014--2020},
  author={Cullmann, Claire and Hoppe-Seyler, Karin and Dymalla, Susanne and Lohrey, Claudia and Scheffner, Martin and Dürst, Matthias and Hoppe-Seyler, Felix}
}
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