Regulation of urokinase plasminogen activator system in tumor cells

Madunić, Josip (2015) Regulation of urokinase plasminogen activator system in tumor cells. Doctoral thesis, Faculty of Science > Department of Biology.

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Urokinase plasminogen activator (uPA) system regulates extracellular matrix remodeling by activating ubiquitous protease plasmin. The system is involved in various physiological and pathological processes and its regulation is cell specific involving the regulation of proenzyme, its inhibitors and receptor. This thesis describes the regulation of uPA system in A1235 glioblastoma cells, deficient in alkylation damage repair, after the treatment with poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor and alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). MNNG has induced an increase in uPA activity in the narrow range of concentrations, under the conditions of high viability and the cell cycle arrest. In these experimental conditions, inhibition of PARP-1 has modulated induced uPA activity influencing the process of DNA repair. Increase in uPA activity was a consequence of change in the balance between uPA and its inhibitor PAI-1 expression and involved various signaling pathways. In the second part of this research, we found that sodium salicylate (NaS), a derivative of aspirin, has changed the expression of uPA and PAI-1 in MDA MB-231 breast cancer cells and inhibited uPA activity in a dose- and time-dependent manner. NaS has also inhibited the expression of αV i β5 integrin subunits, arrested cell growth and induced morphological changes. These results altogether confirmed the complex nature of uPA system regulation which is cell specific and involves various signaling pathways.

Item Type: Thesis (Doctoral thesis)
Keywords: tumor cells, urokinase plasminogen activator, poly(ADP-ribose) polymerase-1, sodium salicylate, DNA damage, signal pathways
Supervisor: Matulić, Maja
Date: 2015
Number of Pages: 140
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 04 Mar 2015 09:43
Last Modified: 04 Mar 2015 09:43

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