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Identifier 000443446
Title The effect of transcriptional repressor Erf loss in prostate cancer
Alternative Title Η επίδραση της απώλειας του μεταγραφικού καταστολέα ERF στον καρκίνο του προστάτη
Author Καδιανάκη, Αικατερίνη Λ.
Thesis advisor Μαυροθαλασσίτης, Γεώργιος
Reviewer Παπαματθαιάκης, Ιωσήφ
Τσατσάνης, Χρήστος
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.
Language English
Subject Mouse model
Tumor suppressor
Ζωικό μοντέλο
Ογκοκατασταλτικό γονίδιο
Issue date 2021-11-26
Collection   School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/9/b/b/metadata-dlib-1636458449-891998-27850.tkl Bookmark and Share
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