Research Report 2000 - MDC

transplants. We are now generating
therapeutic vectors expressing
apoptosis-inducing genes under the
control of the YB-1 promoter.
Regulation of human
papillomavirus 18 oncogene
transcription
E. Grinstein, I. Weinert, W. Jia
in cooperation with R. Kraft (MDC),
S. Hauptmann and M. Dietel (Berlin)
High risk human papillomaviruses e.g.
HPV18 and HPV16 are causative
agents of squamous cell carcinomas of
the cervix uteri and cervical cancer is
the leading cause of death in India and
China. Furthermore, the frequencies
of cervical cancers are markedly
increased in HIV- infected women. In
the last two years, we have studied the
transcription regulation of HPV18
oncogene expression. The cell cycleregulated
HPV18 enhancer factor p92
was purified and its amino acid
sequence has been determined. We
have used a p92-GST Fusion protein
and have shown that p92 binds in a
sequence-specific fashion to the
HPV18 enhancer. Antisense knock-out
experiments have revealed that p92 is
a key regulator of HPV18 oncogene
transcription. Using DNase I, we have
shown that p92 is involved in
regulating chromatin accessibility of
the HPV18 enhancer. In addition, we
have discovered that, in high grade
squamous intraepithelial lesions, p92
expression is deregulated suggesting
that in vivo deregulated p92
expression levels are a critical event
in cervical carcinogenesis. These
results have been submitted for
publication.
74
Selected Publications
Bargou, R.C., Jürchott, K., Metzner,
S., Wagener, C., Dietel, M., Guski, H.,
Dörken, B., and Royer, H.-D. (1997)
Nuclear localization and increased
levels of transcription factor YB-1 in
primary human breast cancers are
associated with intrinsic MDR1 gene
expression. Nat. Med. 3, 447-450.
Bargou, R.C., Emmerich, F.,
Krappmann, D., Bommert, K.,
Mapara, M.Y., Arnold, W., Royer,
H.D., Grinstein, E., Scheidereit, C.,
and Dörken, B. (1997) Constitutive
NF-kappa B- RelA activation is
required for proliferation and survival
of Hodgkin’s disease tumor cells. J.
Clin. Invest. 100, 1-9.
Jundt, F., Leng, C., Krappmann, D.,
Emmerich, F., Mapara, M.Y.,
Bommert, K., Royer, H.-D.,
Scheidereit, C., and Dörken, B. (1999)
Hodgkin/Reed-Sternberg cells induce
fibroblasts to secrete eotaxin, a potent
chemoattractant for T cells and
eosinophils. Blood 94, 2065-2071.
Royer, H.-D., Grinstein, E., and Janz,
M. (1999) Regulation des Zellzyklus
und therapeutische Implikationen. Der
Onkologe 5, 884-890.
Patent Applications
Holm, P.S., Royer, H.-D., Dietel, M.,
Bergmann, S., Lage, H., Jürchott, K.,
Braandt, A., and Ladhoff, A. (1999)
Mittel zur Behandlung maligner
Erkrankungen unter Verwendung des
Proteins YB-1. Aktenzeichen 199 29
569.7.
Wolff, G., Royer, H.-D., Woischwill,
C., Janz, M., Schumacher, A., and
Dörken, B. (1999) Gentransfervektor
für die Diagnostik und die Therapie
von malignen Tumoren. Aktenzeichen
198 60 602.8.
Bergmann, S., Jürchott, K., Brand, K.,
Holm, P.S., and Royer, H.-D. (1999)
Mittel zur Diagnose und Therapie
maligner Erkrankungen. Aktenzeichen
199 29 747.9.
Weitz, J., Royer, H.-D., Stöhr, M.,
Kopun, M., and Napierski, I. (1999)
Nuclear Inhibitor I-92 and its use for
the production of a medicament. U. S.
Patent Application No. 08/183,909.
Weitz, J., Royer, H.-D., Stöhr, M.,
Kopun, M., and Napierski, I. (1999)
Nuclear Inhibitor I-92 and its use for
the production of a medicament.
Europäische Patentanmeldung Nr. 92
115 730.1.
Structure of the Group
Group leader
Dr. Hans-Dieter Royer
Scientists
Dr. Martin Janz
Dr. Karsten Jürchott
Dr. Edgar Grinstein*
Graduate students
Stephan Bergmann
Ying Shan
Christiane Woischwill
(clinical cooperation, Dr. G. Wolff)
Wentao Jia
A. Schmid
Technical assistants
Ingeborg Weinert
Katrin Jäger
(clinical cooperation, Dr. G. Wolff)
Gerlinde Grelle
*part of the period reported