Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 57
Expression of the E2F family of transcription factors and its clinical relevance in a test
set of 78 ovarian cancer patients.
Daniel Reimer, Susann Sadr, Annemarie Wiedemair, Nicole Concin, Gerda Hofstetter,
Christian Marth and Alain G. Zeimet
Department of Obstetrics and Gynaecology, Medical University Innsbruck, Austria
Email: daniel.reimer@uibk.ac.at
The E2F family of transcription factors, firstly discovered as a cellular activity that could bind
to and activate the adenoviral E2 gene promoter, plays a pivotal role in the regulation of
cellular proliferation by controlling the expression of genes required for both cell cycle
progression and apoptosis. Based upon sequence homology and function, eight distinct
members of E2F transcription factors have been distinguished until to date. E2F family is
roughly subdivided into proliferation-promoting (E2F1, E2F2, E2F3a) and –inhibiting
(E2F3b, E2F4, E2F5, E2F6) transcription factors. E2F7 and the recently described E2F8,
represent a distinct subgroup through their unique structure predominantly inhibiting E2Fdriven
gene promoters. Whereas, E2F family members generally require binding to its
dimerization partner DP for transcriptional activity, E2F7 and E2F8 lack the dimerization
domain.
The regulation of E2F transcription factors is closely associated with the function of the
retinoblastoma family of tumour suppressors, the retinoblastoma binding protein (pRB), p107
and p130. In the last decade various alterations of distinct components of the pRB-E2F
pathway were found to be associated with tumour progression through increase of
proliferation or inhibition of apoptosis. However, no data on the role of E2F family members
are available in tumour biology of ovarian cancer. Here we describe an expression study of
E2F transcription factors in various human ovarian cancer cell lines and its clinical relevance
was examined in a training set of 78 ovarian cancer patients.
Expression levels of E2F1, E2F2 and E2F8 were elevated in all the ovarian cancer cell lines
studied when compared with peritoneal mesothelial cells (PMC) and ovarian surface
epithelial cells (OSE). Interestingly, interferon-gamma treatment showed a time-dependent
reduction of the activating transcription factors E2F1 and E2F2 in HTB-77 cells, indicating
that the antiproliferative effect of interferon-gamma is mediated at least in part through downregulation
of proliferation-promoting E2F members. High expression of E2F1, E2F2 and
E2F8 was found to be associated with poor overall survival and large residual disease after
initial debulking surgery in ovarian cancer patients, whereas high expression levels of E2F4, a
repressive transcription factor, was associated with favourable overall survival.
Taken together, these data suggest that E2F transcription factors, mainly E2F1, E2F2, E2F8
and E2F4, play a pivotal role in tumour biology of ovarian cancer and may be candidates for
specific therapeutic targets.
- 560 -