Nucleolin as activator of human papillomavirus type 18 oncogene transcription in cervical cancer
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Authors
Grinstein, Edgar
Wernet, Peter
Snijders, Peter J.F.
Rösl, Frank
Weinert, Inge
Jia, Wentao
Kraft, Regine
Schewe, Christiane
Schwabe, Michael
Hauptmann, Steffen
Issue Date
2002-10-21
Type
Article
Language
en_US
Keywords
Tumor Virus , Carcinogenesis , Cell Cycle , Proliferation , Chromatin
Alternative Title
Abstract
High risk human papillomaviruses (HPVs) are central to the development of cervical cancer and the deregulated expression of high risk HPV oncogenes is a critical event in this process. Here, we find that the cell protein nucleolin binds in a sequence-specific manner to the HPV18 enhancer. The DNA binding activity of nucleolin is primarily S phase specific, much like the transcription of the E6 and E7 oncoproteins of HPV18 in cervical cancer cells. Antisense inactivation of nucleolin blocks E6 and E7 oncogene transcription and selectively decreases HPV18+ cervical cancer cell growth. Furthermore, nucleolin controls the chromatin structure of the HPV18 enhancer. In contrast, HPV16 oncogene transcription and proliferation rates of HPV16+ SiHa cervical cancer cells are independent of nucleolin activity. Moreover, nucleolin expression is altered in HPV18+ precancerous and cancerous tissue from the cervix uteri. Whereas nucleolin was homogeneously distributed in the nuclei of normal epithelial cells, it showed a speckled nuclear phenotype in HPV18+ carcinomas. Thus, the host cell protein nucleolin is directly linked to HPV18-induced cervical carcinogenesis.
Description
Citation
Grinstein, E., Wernet, P., Snijders, P. J., Rösl, F., Weinert, I., Jia, W., Kraft, R., Schewe, C., Schwabe, M., Hauptmann, S., Dietel, M., Meijer, C. J., & Royer, H. D. (2002). Nucleolin as activator of human papillomavirus type 18 oncogene transcription in cervical cancer. The Journal of experimental medicine, 196(8), 1067–1078. https://doi.org/10.1084/jem.20011053
Publisher
The Journal of Experimental Medicine