Dissertation committee:
Δημήτριος Ι. Στραβοπόδης Επίκουρος Καθηγητής (Επιβλέπων), Λουκάς Χ. Μαργαρίτης Ομότιμος Καθηγητής, Ισιδώρα Σ. Παπασιδέρη Αναπληρώτρια Καθηγήτρια
Summary:
In the context of the present PhD thesis, we investigated the anti-oncogenic
properties of specific members of the benzoquinone ansamycin family of
antibiotics in human bladder cancer cell lines of diverse malignancy grade and
genetic background. The molecular techniques implemented in order to assess the
biological effects of ansamycins on bladder cancer cell cultures in vitro were:
fluorescence activated cell sorting (FACS) experiments, MTT tests, Western
blottings, semi-quantitative RT-PCRs, electrophoretic mobility shift assays
(EMSA), immunofluorescence and confocal microscopy, scratch wound assays,
autophagy detection and 2DGE (2-dimensional gel electrophoresis), followed by
proteomic analysis. The experimental data presented herein display the response
mechanisms of bladder cancer cells due to drug-induced Hsp90 inhibition and the
dose-dependent downregulation of its individual protein-clients. We have
unveiled the multidimensional effect of Hsp90 inhibition upon the whole
spectrum of cellular physiology by containment of various signaling cascades,
furthermore resulting in the repression of the hallmark traits of cancer, while
we also revealed new biomarkers for the clinical staging of human urinary
bladder cancer. Conclusively, our experimental data reflect the prominent
therapeutic value and clinical importance of benzoquinone ansamycins, denoting
their central role in modern targeted chemotherapy of bladder cancer, and
likely in other types of human malignancy.
Keywords:
Cancer, Urinary bladder, Heat shock protein 90 (Hsp90), Benzoquinone ansamycins (BA), Signal transduction
