No 11 /October 22, 2002
MDC Researchers Detect Mechanism by which Human Papillomavirus Type 18 Triggers Cervical Cancer - Second most Common Cancer in Women
More than 500,000 women are diagnosed with cervical cancer
each year and almost 200,000 die from it. Next to breast cancer it is the
second most common malignancy in women. Human papilloma viruses (HPV), usually
harmless viruses which cause warts, play a central role in the onset of
cervical cancer. HPV types 16 and 18 are two representatives of the high risk
human papillomaviruses which cause cervical cancer. Dr. Edgar Grinstein and Dr.
Hans-Dieter Royer (Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch
and Heinrich Heine University Düsseldorf, Germany) have been able to show how a
healthy cell is transformed into a tumour cell after becoming infected with HPV
18. Their findings which are
the result of a collaboration with researchers from the University Amsterdam,
The Netherlands, the German Cancer Research Center, Heidelberg, and the
Charité, Campus Mitte, Medical School of the Humboldt University of
Berlin/Germany have just been published in the renowned American Journal of
Experimental Medicine (Volume 196, Number 8, October 21, 2002, 1-13, http://www.jem.org/cgi/doi/10.1084/jem.20011053)*
Dr. Grinstein and Dr. Royer have been able to show that a human protein called nucleolin triggers the development of cervical cancer. This protein usually plays a crucial role in cell division and other biological activities. As the virus integrates its genome into the DNA of the host cells during infection, nucleolin is able to bind to control elements of the virus (enhancer) and, in consequence, activates the expression of two oncogenes (E6 and E7). The researchers have been able to demonstrate that this process takes place during a specific phase of cell division, the so-called S phase. The S Phase is a key process of cell division in the healthy organism. During this phase the chromosomal material of the cell is replicated so that the new cell also possesses the whole genetic make-up of the organism. However, the cell continuously replicates once the viral oncogenes have been activated and so the new cell is transformed into a cancer cell. The process of turning a normal cell into a tumour cell is complex and nucleolin plays a key role in this process.
HPV16 and HPV 18 are most commonly found in invasive cervical carcinomas. However, HPV 18 is most prevalent in so called adenocarcinomas of the cervix. This tumour is highly aggressive according to Dr. Royer. Also the researchers have been able to show that nucleolin is evenly distributed among healthy epithelial cells. However, the nucleolin is much less homogeneous in precancerous and cancerous tissue from the cervix. These findings will perhaps make it possible to develop a new diagnostic test to detect cervical cancer at an early stage. The researchers are optimistic that they will be able to detect the cause of the uneven distribution of nucleolin in cancer cells and thus make it possible to develop new therapies for the treatment of cervical carcinomas in the future.
*Nucleolin
as Activator of Human Papillomavirus Type 18 Oncogene
Transcription in Cervical Cancer Edgar Grinstein,1 Peter Wernet,1
Peter J. F. Snijders,2 Frank Rösl,3 Inge Weinert,4
Wentao Jia,4 Regine Kraft,4 Christiane Schewe,5
Michael Schwabe,5 Steffen Hauptmann,5 Manfred Dietel,5
Chris J.L.M. Meijer,2 and Hans-Dieter Royer,1,4 1 Institut für Transplantationsdiagnostik
und Zelltherapeutika, Heinrich-Heine Univerisität Düsseldorf, 40225 Düsseldorf,
Germany 2 Department of Pathology, Vrije
Universiteit, Medical Center, 1007 MB Amsterdam, Netherlands 3 Angewandte Tumorvirologie,
Deutsches Krebsforschungsforschungs, 69120 Heidelberg, Germany 4 Max-Delbrück-Centrum für
Molekulare Medizin (MDC) Berlin-Buch, 1325 Berlin, Germany 5 Institut für Pathologie,
Charité, Campus Mitte, Medizinische Fakultät der Humboldt-Universität zu
Berlin, 10117 Berlin., Germany
Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
http://www.mdc-berlin.de/englisch/about_the_mdc/public_relations/e_index.htm