| Abstract |
Prostate cancer (PCa) is one of the commonest in incidence cancer types among the men of the West World,
as it is considered to affect about 33.3%of their population, as a result of the aging population of Earth. PCa
comprises a disease, that includes hyperproliferation of the prostatic epithelial cells and multiple stages can
be detected, depending on the severity and the aggressiveness of each case. Among the other etiological
factors for the disease, genetic aberrations represent the most significant ones. Importantly, 50% of prostate
cancer patients carry the TMPRSS2:ERG fusion on Chromosome 21. Apart from ERG, other transcriptional
activators of the same family (Ets transcription factor family) are involved in gene fusions, accounting for
70% of the total prostate cancer cases, when summed.
Erf, a transcriptional repressor of the same family, has the same target genes as Erg according to previous
studies. Thus, Erf loss could recapitulate in vivo Erg gain and consequently be a driver of prostate cancer
initiation and progression. Unfortunately, none of the up to now published genetically engineered mouse
models (Mus Musculus) can accurately recapitulate human disease, in terms of bone metastasis, a mouse
model of Erf loss can provide a promising solution to this problem. Provided the publication of controversial
data, in terms of whether TMPRSS2:ERG fusion can by itself lead to prostate cancer, apart from tissuespecific Erf deletion, we proceed to concomitant tissue specific Pten heterozygous deletion in our mouse
model, which is considered as a permissive event for PCa initiation.
Our up to date data suggest that tissue-specific homozygous Erf deletion can lead to hyperplasias of the
murine prostate beginning from the age of 30 weeks or older, with an evaluated penetrance of about 50%.
Also, study of Erf loss in Pten heterozygous loss background revealed a possible acceleration in cancer
initiation, as well as aggravation of the phenotype, without excluding the possibility of a synergistic effect
between the two factors. As far as metastatic phenotype is concerned, no metastatic lesions were observed
until the age of nine months, but samples of older age remain to be tested.
Finally, we proceed to isolation of primary prostatic epithelial cells from mice and studied their behavior in
ex vivo short- and long-term cell culture. Cells were analyzed for their survival ability, as well as their
proliferation potential before and after freezing. Also, molecular biomarkers were employed to investigate
the maintenance of different epithelial cell types balance through time and before and after freezing.
Acquired knowledge will be valuable for further molecular analysis of Erf loss, as far as the alterations in
transcriptome of prostate epithelial cells, and subsequently their transformation to cancer cells are
concerned.
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