diplomsko naloga
Aleš Šket (Author), Janko Kos (Mentor), Tea Lanišnik-Rižner (Co-mentor)

Abstract

Rak endometrija (rak maternične sluznice) je četrta najpogostejša oblika raka pri ženskah v Zahodni Evropi in ZDA. Pojavlja se predvsem pri ženskah v obdobju po menopavzi. Nekontrolirano vnetje, povezano s povišano koncentracijo prostaglandinov (PG) v endometrijskem tkivu, lahko vodi do razvoja raka endometrija. Prostaglandini stimulirajo celično proliferacijo, celično adhezijo, migracijo in angiogenezo ter s tem pospešijo rast tumorjev. Retinojska kislina ima zaščitno vlogo, saj preko receptorjev RAR in RXR pomaga pri diferenciaciji celic. Protein AKR1B1 je udeležen v reakcijah nastanka vnetnih mediatorjev, saj deluje kot prostaglandin sintaza, ki pretvarja PGH2 v PGF2α. Z redukcijo aldehida 4- hidroksinonenala, ki nastane s peroksidacijo lipidov, AKR1B1 posredno stimulira NF-κB, kar lahko vodi v aktivacijo citokinov in vnetnih mediatorjev, kot je ciklooksigenaza-2 (COX-2). Protein AKR1B10 katalizira redukcijo retinala v retinol in tako posredno preprečuje nastanek retinojske kisline, ki je vključena v uravnavanje celične proliferacije in diferenciacije. AKR1B10 katalizira tudi redukcijo izoprenil aldehidov. S tem uravnava prenilacijo GTP-az ter tako vpliva na proliferacijo in apoptozo celic. V okviru diplomske naloge smo proučili prisotnost AKR1B1 in AKR1B10 v tumorskem in kontrolnem endometriju. V 30 parih vzorcev proteinov, izoliranih iz tumorskega in kontrolnega tkiva endometrija smo z metodami poliakrilamidne gelske elektroforeze, prenosa western in z detekcijo s specifičnimi protitelesi ugotavljali prisotnost proteinov AKR1B1 in AKR1B10. Zaznali smo statistično značilno nižjo količino obeh proteinov v tumorskih vzorcih. Z imunohistokemijskim barvanjem smo prisotnost obeh proteinov potrdili tudi na celični ravni. AKR1B1 in AKR1B10 se nahajata v citoplazmi epitelijskih celic rakavega endometrija.

Keywords

rak endometrija;prostagladini;proteini;ženska;menopavza;

Data

Language: Slovenian
Year of publishing:
Source: Ljubljana
Typology: 2.11 - Undergraduate Thesis
Organization: UL MF - Faculty of Medicine
Publisher: [A. Šket]
UDC: 618.1
COBISS: 30586073 Link will open in a new window
Views: 310
Downloads: 58
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Other data

Secondary language: English
Secondary title: Detection of proteins AKR1B1 and AKR1B10 in endometrial cancer
Secondary abstract: Endometrial cancer is the fourth-most-common cancer in women in western Europe and USA. The majority of cases occur in post-manopausal women. Uncontrolled inflammation, associated with increased production of prostaglandins (PG) in endometrial tissue, can lead to development of endometrial cancer. The prostaglandins stimulate cell proliferation, cell adhesion, cell migration and angiogenesis and therefore accelerate tumor growth. Retinoid acid by binding to the retinoic acid receptor (RAR) and the retinoid X receptor (RXR) stimulates cell differentiation, and thus has protective role. Enzyme AKR1B1is involved in synthesis of inflammatory mediators and it acts as a PG synthase that convert PGH2 to PGF2α. AKR1B1 catalyzes the reduction of lipid peroxidation products, such as 4-hydroxynonenal (HNE) and indirectly stimulates transcription factor NF-κB, which then stimulates expression of cytokines and inflammatory mediators, such as cyclooxygenease-2 (COX-2). Enzyme AKR1B10 catalyzes the reduction of retinals to retinols and indirectly prevents synthesis of retinoid acid, which is involved in cell proliferation and cell diferentiation. AKR1B10 catalyzes also reduction of isoprenyl aldehydes and is involved in prenylation of small GTPases, which regulate cell proliferation and apoptosis. In this research we analyzed presence of AKR1B1 and AKR1B10 in samples of cancerous and adjacent noncancerous endometrial tissues. We investigated the AKR1B1 and AKR1B10 protein levels in 30 paired samples by SDS – PAGE electrophoresis, western blot analysis and chemiluminiscence detection. Both protein levels were significantly decreased in tumorous tissues, compared to controls. We confirmed presence of both proteins in endometrial cancer also at the cellular level with immunohistochemical staining. AKR1B1 and AKR1B10 were located predominantly in the cytoplasm of the epithelial cells of cancerous endometrial tissue.
Type (COBISS): Undergraduate thesis
Thesis comment: Univ. v Ljubljani, Fak. za farmacijo
Pages: 40 f.
ID: 12056026