Correlation study between cycloxygenase 2 expression and telomerase activity in colorectal cancer

Postgraduate Thesis uoadl:2884327 143 Read counter

Κατεύθυνση Χειρουργική Ογκολογία
Library of the School of Health Sciences
Deposit date:
Ayiomamitis Georgios
Supervisors info:
Θεοδόσιος Θεοδοσόπουλος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπων
Γεώργιος Πολυμενέας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Γ. Τούτουζας, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Μελέτη της σχέσης ανάμεσα στη γονιδιακή έκφραση της κυκλοξυγενάσης 2 και της ενεργότητας της τελομεράσης στον ορθοκολικό καρκίνο
Translated title:
Correlation study between cycloxygenase 2 expression and telomerase activity in colorectal cancer
Cyclooxygenase 2 (COX-2) is involved in the initial steps of colorectal cancer (CRC) formation, playing a key role in the catalysis of arachidonic acid to prostaglandin E2 (PGE2). The human telomerase reverse transcriptase (hTERT) also plays an important role in colorectal cancer growth, conferring cells sustained proliferation and survival. Although hTERT induces COX-2 expression in gastric and cervical cancer, their interaction has not been investigated in the context of CRC. COX-2, PGE2 levels and telomerase activity, were evaluated by immunohistochemistry, ELISA and TRAP assay in 49 colorectal cancer samples. PTGS1, PTGS2, PTGES3, TERT mRNA and protein levels were investigated using RNA-seq data from the TCGA and the HPA projects. A multi-omics analysis comparison was performed between PTGS2 and TERT. COX-2 expression was positive in 40/49 CRCs, bearing cytoplasmic and heterogeneous staining, and moderate to intense intensity. COX-2 staining was mainly detected in the stroma of the tumor cells and the adjacent normal tissues. PGE2 expression was lower in CRC compared to the adjacent normal tissue, and inversely proportional to telomerase activity in right colon cancers. COX-1 and COX-2 were anti-correlated to TERT. COX-2 expression was also higher among BRAFmut CRCs. The promoter regions of COX-2 and TERT were reversely methylated. Our data support that COX-2 is involved in the early stages of colorectal cancer development, initially affecting the tumor’s stromal microenvironment, and subsequently the epithelial cells. They also highlight the inverse correlation between COX-2 expression and telomerase activity in CRC, due differential methylation in their promoters.
Main subject category:
Health Sciences
Colorectal cancer, COX-2, PGE2, hTERT
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