Ispitivanje aktivnosti enzima antioksidativne zaštite, matriks metaloproteinaza-2 i -9 i pokazatelja ćelijske smrti u tkivu pacijentkinja sa karcinomom dojke
Analysis of activity of antioxidative enzymes, matrix metaloproteinases-2 and -9 and cell death parameters in tissue of breast cancer patients
Author
Radenković, Sandra S.Mentor
Gopčević, KristinaCommittee members
Konjević, GordanaIsaković, Aleksandra
Milošević, Zorica
Jurišić, Vladimir
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Show full item recordAbstract
Uvod: Obzirom da je aktivnost laktat dehidrogenaze (LDH) i malat dehidrogenaze
(MDH) povezana sa procesima proliferacije i invazije tumora, odredjivanje distribucije
njihovih izoenzima važno je u procesu metabolizma tumorske ćelije. Dugo se smatralo da
enzimi antioksidativne zaštite, kao što su superoksid dismutaza (SOD) i katalaza (CAT),
štite ćelije od kancerogeneze. Medjutim, pokazano je da su CAT i SOD uključene u
procese izbegavanja ćelijske smrti i proliferacije, zbog čega predstavljaju važne
medijatore u biologiji karcinoma dojke. Sve češće povezivanje mamografskih
karakteristika sa histopatološkim markerima i enzimima, stvara novu klasifikaciju
pacijentkinja sa karcinomom dojke u cilju adekvatnog individualnog pristupa. Pored
povećane aktivnosti enzima antioksidativne zaštite, u karcinomima dolazi do poremećaja
ekspresije pokazatelja ćelijske smrti kao što su STAT3, ciklin D1 i Bcl-2. Obzirom na
porast incidence karcinoma dojke u svetu, javlja se sve veća potreba za definisanje...m
panela tumorskih markera koji bi pouzdano mogli da identifikuju karcinom dojke sa
mogućom tendencom recidiva. Podaci pokazuju da marker za karcinom dojke može biti
medju proteinima koji učestvuju u procesu tumorske progresije kao što su MMP-2,
MMP-9 i TIMP1.
Cilj: Iz tih razloga, cilj ovog rada je bio utvrdjivanje aktivnosti enzima antioksidativne
zaštite (SOD, CAT), anaerobnog metabolizma (LDH, MDH), invazivnosti (MMP-2,
MMP-9, TIMP1) i ekspresije pokazatelja ćelijske smrti (pSTAT3, bcl-2, Ciklin D1) u
tumorskom tkivu i njihovog odnosa sa kliničko-patološkim karakteristikama tumora, kao
i sa mamografskim nalazom bolesnica sa karcinomom dojke.
Materijal i metode: U radu je analizirano 75 uzoraka tumorskog i 75 uzoraka okolnog
peritumorskog tkiva bolesnica sa histopatološki potvrđenim karcinomom dojke.
Aktivnost MMP-2 i MMP-9 određivana je metodom želatin zimografije, dok je aktivnost
SOD, CAT, LDH i MDH određivana odgovarajućim spektrofotometrijskim metodama...
Introduction: Lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) activity
is associated with highly invasive and metastatic breast cancer. It was long thought that
the antioxidative enzymes such as superoxide dismutase (SOD) and catalase (CAT),
protect cells against carcinogenesis. However, it has been shown that SOD and CAT play
role in processes of proliferation and cell death. Association of enzyme profile and
mammographic features provide insights into the biological processes in breast cancer
and could be of use in defining novel biomarkers and potential therapeutic targets.
Together with increased activities of antioxidative enzymes, cancers have altered
expression of cell death parameters such as STAT3, Bcl-2 and cyclin D1. Since the
incidence of breast cancer is increasing, it is necessary to find more tumor markers for
breast cancer patients with high risk of recurrence. The proteins of tumor progression
such as MMP-2, MMP-9 and TIMP1 could be possible tumor markers.
A...im: The aim of this study was to examine the activity of antioxidative (SOD, CAT),
anaerobic metabolism (LDH, MDH), invasivness (MMP-2, MMP-9) enzymes and
expression of cell death parameters (TIMP1, STAT3, cyclin D1, Bcl-2) and their relation
with clinico-pathologic and mammographic characteristics of breast cancer patients.
Material and methods: In this study we analyzed tumor and adjacent tissue samples of
75 breast cancer patients. We examined the activity of MMP-2 and MMP-9 by gelatin
zymography, while SOD, CAT, LDH and MDH activity was assayed
spectrophotometrically. Distribution of isoforms was determined with direct and reverse
electrophoretic zymography. Expression of TIMP1, STAT3, cyclin D1 and Bcl-2 was
assessed in tumor lysates by Western blotting. Mammograms were evaluated according
to the American College of Radiology Breast Imaging Reporting and Data system
(BIRADS). Significance of differences of the obtained results was analyzed by the T test,
Wilcoxon rank sum test and Mann–Whitney U-test.
Results: The LDH5 izoenzyme was detected in tumor tissue of breast cancer patients.
The activity of MDH, m-MDH, CAT and m-SOD in tumor tissue of breast cancer patients significantly increases compared to adjacent patient tissue...
Faculty:
Универзитет у Београду, Медицински факултетDate:
06-06-2013Projects:
- Molecular, biochemical and immunological tumor diagnosis (RS-MESTD-Basic Research (BR or ON)-175056)