12 results on '"Wnt signaling pathway"'
Search Results
2. SFRP4 promoter methylation and protein expression in human brain tumors
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Drmić, Denis, Kafka, Anja, and Hranilović, Dubravka
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signalni put Wnt ,imunohistokemija ,Wnt signaling pathway ,SFRP family ,PRIRODNE ZNANOSTI. Biologija ,MS PCR ,astrocitomi ,immunohistochemistry ,NATURAL SCIENCES. Biology ,astrocytoma ,obitelj SFRP - Abstract
Astrocitomi su najčešća vrsta glioma, a klasificirani su u tri gradusa: difuzne astrocitome, anaplastične astrocitome i glioblastome. Signalni put Wnt esencijalan je u mnogim biološkim procesima, stoga njegova aberantna aktivnost ima jednu od ključnih uloga u tumorigenezi. Obitelj proteina SFRP (engl. Secreted Frizzled-Related Protein) modulira Wnt signalizaciju. U različitim tumorima se pokazalo da su ovi geni transkripcijski utišani hipermetilacijom promotorske regije, što u konačnici vodi nekontroliranom prepisivanju onkogena. Cilj rada bio je utvrditi dolazi li do različite učestalosti promjena metilacijskog statusa promotora gena i razine ekspresije proteina SFRP4 kod različitih histoloških gradusa astrocitoma. Ekspresija proteina SFRP4 detektirana je metodom imunohistokemije, dok je metilacijski status promotora gena istih uzoraka ispitan metodom MS PCR. Statističkom analizom utvrđeno je da se povećanjem gradusa tumora smanjuje ekspresija proteina SFRP4 u astrocitomima (p=0,008), što ukazuje da bi SFRP4 mogao djelovati kao tumor supresor inhibirajući aktivnost signalnog puta Wnt te sprječavajući nastanak i progresiju ovih tumora. Analiza metilacije otkrila je da 72,7% difuznih astrocitoma ima metiliran promotor gena SFRP4, dok kod viših gradusa metiliranost promotora nije detektirana. Utvrđena je statistički značajna razlika u metilacijskom statusu gena SFRP4 između pojedinih stupnjeva malignosti astrocitnih tumora (p
- Published
- 2022
3. Alterations of DVL1 gene in human intracranial meningioma
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Dragičević, Katarina, Pećina-Šlaus, Nives, and Blažević, Sofia Ana
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signalni put Wnt ,Wnt signaling pathway ,intrakranijalni meningeom ,DVL1 ,domena PDZ ,PRIRODNE ZNANOSTI. Biologija ,NATURAL SCIENCES. Biology ,PDZ domene ,intracranial meningeoma - Abstract
Meningeomi su najčešći primarni tumori središnjeg živčanog sustava, koji u manje od 20% slučajeva mogu pokazivati agresivnost, recidive i metastaze. Među signalnim putevima uključenima u progresiju meningeoma nalazi se i signalni put Wnt čiji je središnji medijator protein DVL1 koji inhibira djelovanje destrukcijskog kompleksa za razgradnju ß-katenina. Uslijed toga se ß-katenin nakuplja u citoplazmi i premješta u jezgru gdje potiče transkripciju onkogena. Budući da je dokazana uloga proteina iz porodice DVL u progresiji tumora središnjeg živčanog sustava, cilj je ovog rada bio istražiti utjecaj promjena gena DVL1 na progresiju intrakranijalnih meningeoma čovjeka. Izolirana je DNA tumora i periferne krvi pacijenata te su amplificirani mikrosatelitni biljeg D1S468 i genska regija koja kodira domenu PDZ, važnu u prijenosu signala Wnt. Gel-elektroforezom umnoženog biljega D1S468 utvrđeno je postojanje mikrosatelitne nestabilnosti u 9,09% uzoraka i gubitka heterozigotnosti u 6,06% uzoraka. Analizom taljenja visoke rezolucije i Sangerovim sekvenciranjem genske regije PDZ, utvrđene su mutacije u 100% sekvenciranih uzoraka. Rezultati analize pokazali su kako dio otkrivenih mutacija ima štetan učinak na biološku funkciju proteina DVL1, mijenjanjem mjesta prekrajanja ili promjenama okvira čitanja sekvence. Ukupni rezultati ovog istraživanja pokazuju ulogu promjena gena DVL1 u razvoju intrakranijalnih meningeomima. Meningiomas are the most common primary tumours of the central nervous system, which in less than 20% of cases may show aggression, recurrence, and metastasis. Among the signalling pathways involved in meningioma progression is the Wnt signalling pathway. The central mediator of the Wnt signalling pathway is the DVL1 protein which inhibits the destruction complex that targets ß-catenin. This results in the accumulation of ß-catenin in the cytoplasm and its translocation to the nucleus, where it promotes oncogene transcription. Since it has been shown that proteins from the DVL family play a role in the progression of central nervous system tumours, the aim of this study was to investigate the influence of alterations in the DVL1 gene on the progression of human intracranial meningiomas. The microsatellite marker D1S468 and the gene region encoding the PDZ domain, important in transducing the Wnt signal, were amplified from DNA that has been isolated from tumour and peripheral blood samples of the patients. Gel electrophoresis of the amplified marker D1S468 revealed the existence of microsatellite instability in 9.09% of samples, loss of heterozygosity in 6.06% of samples. High-resolution melting analysis and Sanger sequencing of the PDZ gene region revealed mutations in 100% of sequenced samples. The results of the analysis showed that some of the detected mutations have a deleterious effect on the biological function of the DVL1 protein, by altering the splice site or shifting the reading frame of the sequence. The overall results of this study demonstrate the role of alterations in DVL1 gene in intracranial meningiomas
- Published
- 2021
4. TCF1 protein expression in diffuse gastric carcinoma
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Fajs, Nina, Nikuševa Martić, Tamara, Paić, Frane, and Šerman, Ljiljana
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Wnt signaling pathway ,diffuse gastric carcinoma ,transcription factors ,genetic abnormalities ,TCF1 - Abstract
Wnt signalni put je uključen u patogenezu brojnih karcinoma, a u nekih je dokazana i pojačana aktivnost nizvodnih transkripcijskih faktora, kao što su proteini TCF/LEF obitelji. Jedna od ovih neoplazmi je i karcinom želuca, koji se histološki prema Laurénovoj klasifikaciji može podijeliti na tri tipa: intestinalni, difuzni i miješani. Karcinom želuca je pri vrhu ljestvice smrtnosti od karcinoma u svijetu, te se brojnim istraživanjima žele otkriti nove terapijske mogućnosti koje bi poboljšale preživljenje i kvalitetu života oboljelih. Cilj ovog istraživanja bilo je dokazati da postoji razlika u ekspresiji TCF1 proteina u normalnom tkivu i tkivu difuznog karcinoma želuca, s pretpostavkom da bi ovaj protein mogao imati ulogu u patogenezi ove vrste karcinoma. Analizirano je 36 uzoraka karcinoma te 43 uzoraka normalnog tkiva prikupljenih iz arhive Kliničkog zavoda za patologiju i citologiju KBC-a Zagreb. Nakon primjene imunohistokemijskog bojanja, napravljena je stereološka kvantitativna analiza te je otkriven značajna razlika (p< 0,05) u ekspresiji TCF1 proteina između stanica u zdravom tkivu i malignih stanica difuznog karcinoma želuca. Ovim rezultatom smo zaključili da bi čimbenik Wnt signalnog puta, protein TCF1, mogao imati ulogu u patogenezi difuznih karcinoma želuca, te su potrebne daljnja istraživanja o ulozi ovog proteina i mogućnosti da se ova spoznaja primjeni u terapijskom postupku., Wnt signal pathway is involved in the pathogenesis of multiple cancer types. Moreover, upregulation of downstream transcription factors, such as TCF/LEF family, is proved in several of them. One of this neoplasms is stomach cancer, which is, according to Laurén classification histologically divided into three categories: intestinal, diffuse and mixed type. Stomach cancer is nearly at the top of the list of leading causes of death from malignant diseases worldwide, and many studies search for new treatment possibilities which would improve survival and quality of life of patients suffering from this disease. The aim of this study was to prove that there is a difference in expression of TCF1 protein between normal tissue and diffuse stomach cancer, with the assumption that this protein may have a role in the pathogenesis of this type of stomach cancer. 36 samples of diffuse gastric carcinoma and 43 samples of normal stomach tissue gathered at the Clinical Institute of Pathology and Cytology of the Zagreb University Hospital Centre were analyzed. After the use of immunohistochemical staining, stereological quantitative analysis was done and a statistically significant difference (p< 0,05) in expression of TCF1 protein between healthy tissue cells and the cells of diffuse gastric carcinoma was found. With this result we concluded that this part of the Wnt signaling pathway could have a role in the pathogenesis of diffuse gastric carcinoma. Further studies are needed to explore the role of TCF1 protein and its potential use in new therapic procedures.
- Published
- 2020
5. Utjecaj izmjene E- i N-kadherina na fosforilacijski status beta-katenina i epitelno-mezenhimsku tranziciju u intrakranijalnim meningeomima
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Bukovac, Anja and Pećina-Šlaus, Nives
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PRIRODNE ZNANOSTI. Biologija ,intrakranijalni meningeomi ,udc:577(043.3) ,epithelial-mesenchymal transition ,E-cadherin ,intracranial meningioma ,Biochemistry. Molecular biology. Biophysics ,E-kadherin ,β-catenin ,signalni put Wnt ,Wnt signaling pathway ,epitelno-mezenhimska tranzicija ,β-katenin ,Biokemija. Molekularna biologija. Biofizika ,NATURAL SCIENCES. Biology ,N-kadherin ,N-cadherin - Abstract
Epitelno-mezenhimska tranzicija (EMT) koju karakterizira kadherinska izmjena, odnosno smanjena ekspresija E-kadherina, a pojačana N-kadherina, ima važnu ulogu u mehanizmima invazivnosti i metastaziranja tumorskih stanica. Klasični signalni put Wnt usko je povezan s procesima EMT, te je poznato da prijelaz β-katenina u jezgru može dovesti do EMT. U ovom istraživanju pokazano je da geni sudionici kadherinske izmjene, CDH1 i CDH2 imaju ulogu u progresiji meningeoma te je zabilježena viša ekspresija N-kadherina u odnosu na E-kadherin. Ekspresija transkripcijskih faktora SNAIL, SLUG i TWIST1 u meningeomima bila je izrazito jača od E- i N-kadherina, a SNAIL i SLUG su bili značajno povezani s višim gradusima (p=0,001) ukazujući na njihovu ulogu u progresiji. Viši gradusi bilježe i porast ekspresije ukupnog β-katenina koju prati i porast ekspresije njegovog aktivnog oblika (p=0,000). Istraživanje ove disertacije donosi prve rezultate genetičkih i proteinskih analiza važnih molekula signalnog puta Wnt i EMT te otkiva njihovu ulogu u intrakranijalnim meningeomima. Također, rezultati istraživanja nude smjernice i nove biljege progresije za buduća istraživanja te otkrivaju nove molekularne mete terapeutskih intervencija. Epithelial to mesenchymal transition (EMT), which is characterized by reduced expression of E-cadherin and increased expression of N-cadherin, plays an important role in the tumor invasion and metastasis. Classical Wnt pathway has a tight link with EMT and it has been shown that nuclear translocation of β-catenin can induce EMT. This research has showed that genes involved in cadherin switch, CDH1 and CDH2, play a role in meningioma progression. Also, increased expression of N-cadherin in relation to E-cadherin was recorded. In meningiomas, transcription factors SNAIL, SLUG, and TWIST1 demonstrated strong expression in relation to E- and N-kadherin. Expression of SNAIL and SLUG was significantly associated with higher grades (p=0,001) indicating their role in meningioma progression. Higher grades also recorded an increased expression of total β-catenin followed by an increased expression of its active form (p=0,000). This dissertation research brings the first results of genetic and protein analyzes of important molecules involved in WNT and EMT signaling pathways and reveals their role in intracranial meningiomas. Results of this research offer guidelines and new markers of progression for future research and reveal new molecular targets of therapeutic interventions.
- Published
- 2020
6. DVL2 and DVL3 protein expression in diffuse gastric carcinomas
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Perković, Marija, Nikuševa Martić, Tamara, Paić, Frane, and Šerman, Ljiljana
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Wnt signaling pathway ,DVL3 ,DVL2 ,diffuse gastric carcinoma ,genetic abnormalities ,Dishevelled proteins - Abstract
Karcinom želuca jedan je od najčešćih tumora na svjetskoj razini, a praćen je visokom razinom smrtnosti. Prema Laurenovoj klasifikaciji iz 1965. godine postoje dva glavna histološka tipa adenokarcinoma želuca, intestinalni i difuzni tip. Genetska podloga ovih karcinoma još uvijek je nedovoljno istražena, a posebno mutacije koje dovode do nastanka difuznog tipa karcinoma želuca. Wnt signalni put uključen je u razvoj različitih vrsta tumora, kao i proteini obitelji Dishevelled koji su njegovi nizvodno smješteni medijatori. Cilj ovog rada bio je analizirati izraženost DVL2 i DVL3 proteina u difuznim karcinomima želuca, s pretpostavkom kako bi oni mogli imati važnu ulogu u razvoju te vrste karcinoma. Ekspresija DVL2 proteina analizirana je u 41 kontrolnom uzorku zdravog tkiva želuca te u 49 uzoraka difuznih karcinoma želuca. Ekspresija DVL3 proteina analizirana je u 49 kontrolnih uzoraka zdravog tkiva želuca te u 50 uzoraka difuznih karcinoma želuca. Uzorci su prikupljeni iz arhive Kliničkog zavoda za patologiju i citologiju KBC-a Zagreb. Nakon imunohistokemijskog bojenja, u kojem su korištena primarna poliklonska protutijela DVL2 i DVL3, rezultati su analizirani semikvantitativnom metodom uz bodovanje postotka pozitivnih tumorskih stanica i intenziteta bojenja. Ekspresija DVL2 proteina u tumorskom tkivu bila je statistički značajno jača u odnosu na zdravo tkivo želuca (p=0.0066). Nasuprot tomu, ekspresija DVL3 proteina nije pokazala statistički značajno jaču ekspresiju u tumorskom tkivu u usporedbi sa zdravim tkivom želuca (p=0.1308). Ekspresija DVL3 proteina statistički je značajno veća u odnosu na DVL2 protein u tumorskom tkivu (p=0.0022), kao i u zdravom tkivu želuca (p, Gastric cancer is one of the most common cancers worldwide, accompanied with high death rate. According to Lauren classification, introduced in 1965, the gastric cancer is classified into two major histological subtypes, intestinal and diffuse type. There is insufficient information concerning genetic abnormalities involved in the pathogenesis of these carcinomas, in particular diffuse type adenocarcinoma. The Wnt signaling pathway and its central mediators, called Dishevelled proteins, play an important role in the development of numerous tumor types. The aim of this study was to analyze DVL2 and DVL3 protein expression in diffuse gastric carcinomas, that we assumed could have potential role in their development. DVL2 expression was analyzed in 41 sample of healthy stomach tissue, as well as in 49 samples of diffuse gastric carcinomas. DVL3 expression was analyzed in 49 samples of healthy stomach tissue, as well as in 50 samples of diffuse gastric carcinomas. The samples were collected from the archives of the Department of Pathology and Cytology of the Zagreb University Hospital Center. After immunohistochemical staining with primary polyclonal antibodies DVL2 and DVL3, the results were analyzed with semiquantitative method which combined the percentage of positive cells and staining intensity. DVL2 protein expression was higher in tumor tissue compared to healthy stomach tissue (p=0.0066). However, DVL3 protein expression was not statistically significantly higher in tumor tissue compared to healthy stomach tissue (p=0.1308). DVL3 expression compared to DVL2 expression was statistically significantly higher in tumor tissue (p=0.0022), as well as in healthy stomach tissue (p
- Published
- 2019
7. Role of WNT signaling pathway in epithelial-mesenchymal transition
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Batarilo, Vjekoslav, Nikuševa Martić, Tamara, Paić, Frane, and Šerman, Ljiljana
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Wnt signaling pathway ,epithelial-mesenchymal transition ,gene expression - Abstract
Epitelno-mezenhimska tranzicija je složeni molekularni proces u kojem dolazi do tranzicije epitelnih stanica u mezenhimske stanice. Stanične promjene koje se događaju tijekom EMT su brojne, a posljedica su prestanka ekspresije gena koji reguliraju epitelni fenotip te preuzimanja transkripcijskog obrasca ekspresije gena koji upravljaju mezenhimskim fenotipom. Neke od tih promjena su prestanak ekspresije E-kadherina, gubitak intercelularnih veza i apikalno-bazolateralne orijentacije stanice itd. Mezenhimske osobine koje stanice stječu su izgled nalik miofibroblastima, pokretljivost i invazivnost, stanice počinju secernirati molekule ekstracelularnog matriksa, manje su podložne aktivaciji apoptoze itd. EMT prisutna je i u fiziološkim i u patofiziološkim procesima. Fiziološki procesi koji su u najvećoj mjeri posljedica EMT su embriogeneza i reparacija tkiva, a patofiziološki procesi u kojima EMT sudjeluju su fibrogeneza i tumorigeneza. Jedan od glavnih puteva koji su zaslužni za aktivaciju ovog staničnog programa je Wnt signalni put. To je evolucijski drevni, konzervirani put. Kategorizirana su tri glavna Wnt puta: jedan kanonski i dva nekanonska. Kod ljudi postoji 19 različitih Wnt proteina, koji su kategorizirani zbog sličnost cisteinskih ostataka na N-terminalnom kraju, a ne prema funkcijama, koje su nota bene, vrlo različite. Wnt ligand veže se za Frizzled receptore te je središnja molekula β-katenin zaslužna za biološke učinke koji se pripisuju Wnt putu. β-katenin translocira se u jezgru gdje se veže za Tcf/Lef transkripcijski faktor i potiče ekspresiju ciljnih gena., Epithelial-mesenchymal transition is a complex molecular process in which epithelial cells transform to mesenchymal cells. Cell changes that occur during EMT are numerous due to loss of epithelial gene expression, and activation of mesenchymal gene expression. Some of those changes are downregulation of E-cadherin expression, loss of epithelial adherens junctions, loss of apical-basolateral polarity etc. Mesenchymal traits which these cells acquire are myofibroblast-like shape, motility and invasiveness, secretion of extracellular matrix, increased resistance to apoptosis etc. EMT occurs both during physiological and pathophysiological processes. Physiological processes, which are to the greatest extent consequence of EMT, are embriogenesis and tissue reparation, while pathophysiological processes in which EMT has role are fibrogenesis and tumorigenesis. One of the major signaling pathway that activates EMT is Wnt signaling pathway. It is evolutionarily ancient and conserved pathway. There are three main Wnt signaling pathway branches; a canonical Wnt pathway and two non-canonical Wnt pathways. There are nineteen distinctive Wnt proteins in humans, which are classified as Wnt based on similarity of their N-terminal cysteine residues, rather than their functions which are quite different. The Wnt ligands bind to Frizzled receptors, while the central molecule β-catenin is responsible for biological effects of Wnt pathway. β-catenin translocates to the nucleus where it binds to Tcf/Lef transcription factor and upregulates expression of target genes.
- Published
- 2017
8. The role of Axin and beta-catenin in Wnt signaling pathway in healthy and meningioma cells
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Grubišić, Ana and Hrašćan, Reno
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Wnt signaling pathway ,Wnt signalni put ,aksin ,Axin ,β-katenin ,BIOTEHNIČKE ZNANOSTI. Biotehnologija ,meningeom ,β-catenin ,meningioma ,BIOTECHNICAL SCIENCES. Biotechnology - Abstract
U ovom radu su prikazane uloge proteina aksina i β-katenina kao ključnih komponenti Wnt signalnog puta u zdravim stanicama i u meningeomima. Osim što ima ulogu kao glavna signalna molekula Wnt puta, β-katenin je također dio međustaničnih spojeva zajedno s E-kaderinom. Do nastanaka i progresije meningeoma dolazi zbog narušavanja međustaničnih spojeva, tako da će smanjen broj molekula stanične adhezije dovesti do povećane proliferacije tumorskih stanica i može doprinijeti invazivnoj sposobnosti meningeoma. Aksin djeluje kao tumor supresor u karcinomu, ali njegova uloga u meningeomima još nije dovoljno razjašnjena. Ipak, gubitak heterozigotnosti AXIN1 gena u meningeomima može upućivati na njegovu ulogu kao tumor supresora te na posljedično smanjenje razine proteina aksina. This paper studies the roles of β-catenin and Axin as key components of Wnt signaling pathway in healthy and meningioma cells. In addition to having a role as a key signaling molecule of Wnt signaling pathway, β-catenin is also a part of the adherens junctions together with E-cadherin. The occurence and progression of meningiomas are due to disrupted adherens junctions and the decrease in cell adhesion molecules may lead to increased tumor cell proliferation and it may contribute to invasive ability of meningioma. Axin acts as a tumor suppressor in cancer, but its role in meningiomas remains unresolved. However, the loss of heterozygosity of AXIN1 gene in meningiomas may indicate its role as a tumor suppressor and suggest consequent down-regulation of its protein.
- Published
- 2017
9. Role of E-cadherin and APC in Wnt signaling pathway of healthy and meningioma cells
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Fižulić, Valentina and Hrašćan, Reno
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Wnt signaling pathway ,Wnt signalni put ,E-kaderin ,BIOTEHNIČKE ZNANOSTI. Biotehnologija ,E-cadherin ,meningeomi ,meningiomas ,BIOTECHNICAL SCIENCES. Biotechnology ,APC - Abstract
Signalni putevi tvore kompleksnu molekularnu mreţu unutar stanice, a njihovo normalno funkcioniranje odrţava staničnu homeostazu. Wnt signalni put je kroz evoluciju sačuvan put koji regulira presudne aspekte tijekom embriogeneze, a poremećaji u njegovom radu mogu dovesti do nastanka tumora. U ovom radu su objedinjena dosadašnja saznanja o ulogama dvaju proteina, E-kaderina i APC-a, u normalnom funkcioniranju Wnt signalnog puta te zabiljeţenim promjenama ovih proteina koje dovode do nastanka ili progresije meningeoma – tumora koji su najčešće spororastući i benigni, koji pripadaju skupini tumora središnjeg ţivčanog sustava te nastaju iz arahnoidalnih stanica. Signaling pathways form a complex molecular network within the cell, and their normal functioning maintains cell homeostasis. Wnt signaling pathway is evolutionary conserved pathway that regulates crucial aspects during embryogenesis, and disorders in its work can lead to development of tumors. In this paper, the present knowledge of the role of two proteins, E-cadhrein and APC, in the normal functioning of Wnt signaling pathway and the observed changes in these proteins leading to the development or progression of meningiomas has been unified. Meningeomas are usually slow-growing benign tumors classified as central nervous system tumors and are formed from arahanoidal cells.
- Published
- 2017
10. Epigenetic changes of the Wnt signaling pathway in tumors of reproductive system
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Hrvojka Janković, Šerman, Ljiljana, Nikuševa Martić, Tamara, and Dolanski-Babić, Sanja
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epigenetic changes ,Wnt signalni put, epigenetske promjene, tumori reproduktivnog sustava ,tumors of the reproductive system ,wnt signaling pathway - Abstract
Epigenetika proučava nasljedne promjene u ekspresiji gena koje se događaju bez promjena u redoslijedu baza molekule DNA. Tri su do danas poznata epigenetska mehanizma: metilacija DNA, modifikacija histona i sinteza malih nekodirajućih RNA. Wnt signalni put se sastoji od heterodimernog receptora sastavljenog od dva tipa transmembranskih proteina na koje se vežu pozitivni ili negativni regulatori staničnog rasta. U slučaju vezanja pozitivnih regulatora, dolazi do translokacije β-katenina u jezgru i aktivacije obitelji o β-kateninu ovisnih transkripcijskih faktora dok vezivanje negativnih regulatora priječi ovaj proces. Jedan od negativnih regulatora Wnt signalnog puta je proteinski produkt gena DACT2 koji djeluje kao tumor supresor, stoga je njegova ekspresija smanjena u kolorektalnom karcinomu i karcinomima želuca. U ovom preglednom radu dan je sistemski prikaz epigenetskih promjena glavnih aktera Wnt signalnog puta i njihov utjecaj na razvoj tumora s naglaskom na tumore reproduktivnog sustava. Posebnu važnost imaju lijekovi koji se primjenjuju u terapiji navedenih tumora, a čiji se terapjiski učinak postiže djelovanjem na epigenetske promjene gena koji kodiraju za glavne proteine Wnt signalnog puta. Izoflavoni koji pripadaju razredu biljnih estrogena, a nalazimo ih u mahunarkama, slanutku i namirnicama od soje, djeluju na signalizaciju putem estrogenskih receptora i mogu modificirati epigenom dojke, uterusa, endometrija, prostate i brojnih drugih organa., Epigenetics studies heritable changes in gene expression that are happening without alterations in the underlying DNA sequence. Up to date, there are three known epigenetic mechanisms: DNA methylation, histone modification and synthesis of small non-coding RNA. Wnt signaling pathway comprises from heterodimer receptor composed of transmembrane proteins onto which positive and negative regulators of cellular growth bind. Binding of positive regulators leads to translocation of β-catenin into the nucleus and activation of β-catenin family- depended transcriptional factors, while binding of negative regulators inhibits this process. One of the negative regulators of Wnt signaling pathway is a protein gene product DACT 2. It acts as a tumor suppressor, hence its expression in colorectal cancer and gastric cancer is diminished. This review demonstrates the systemic look on epigenetic changes among the main effectors of the Wnt signaling pathway and their influence on the tumor development, emphasizing the tumors of reproductive system. Drugs applied in the therapy of the aforementioned tumors are of special importance. Their therapeutic effect is accomplished by the influence on epigenetic changes of genes that code for the main proteins of Wnt signaling pathway. Isoflavones that belong to the class of plant derived compounds with estrogenic activity are found in the pulses, chickpeas, and soy products. Beside their action on the signalization via estrogenic receptors they can also modify epigenome of the breast, uterus, endometrium, prostate and various other organs.
- Published
- 2016
11. Expression of negative regulators of the Wnt signaling pathway in germ cell tumors of the testis
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Žunić, Iris, Šerman, Ljiljana, Ježek, Davor, and Dolanski-Babić, Sanja
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tumori zametnih stanica testisa, Wnt signalni put, SFRP1, SFRP3, imunohistokemija ,Wnt signaling pathway ,immunohistochemistry ,SFRP1 ,SFRP3 ,testis ,germ cell tumors - Abstract
Obitelj proteina SFRP (od engl. secreted frizzled-related protein) najveća je obitelj Wnt signalnog puta. Dosadašnja istraživanja ukazuju na povezanost smanjene ekspresije SFRP proteina i razvoja kolorektalnog karcinoma i karcinoma urotela. Najveći postotak tumora testisa su podrijetla zametnih stanica testisa, a među njima su najčešći seminomi. Obzirom na to da SFRP proteini djeluju kao negativni regulatori Wnt signalizacije, cilj ovog rada bio je ispitivanje ekspresije SFRP1 i SFRP3 proteina u definiranoj kohorti primarnih tumora testisa, seminomskih i neseminomskih/miješanih, metodom indirektne imunohistokemije. Sakupljeni su uzorci tumora zajedno s pripadajućim zdravim tkivom koje je ujedno služilo kao pozitivna kontrola. Rezultati ekspresije oba proteina analizirani su semikvantitativno te statistički obrađeni. Dobiveni rezultati prikazuju statistički značajnu razliku ekspresije SFRP1 (seminomi=0.1 (0.7), neseminomi=0.1 (0.6), kontrola=1 (0), p, Secreted frizzled-related protein (SFRP) family is the largest family of Wnt signaling pathway. Current research efforts clearly outline the relationship between the decreased SFRP protein expression and develepement of colorectal and urothelial carcinomas. The highest percentages of testicular tumors are of those germline origin, among which seminomas represent the most common histotype. Taking into account that SFRP proteins act as negative regulators of Wnt signaling pathway, the purpose of this work was to determine the SFRP1 and SFRP3 protein expression in a defined cohort of primary testicular tumors (including both seminomas and non-seminomas/mixed germ cell), using immunohistochemistry. Tumor samples were collected along with the adjacent normal/benign tissue that was used as a control sample. Protein expressions were measured and the results were semiquantitively analyzed and statistically processed. Obtain results showed statistically significant difference in expression of SFRP1 (seminomas=0.1 (0.7), non-seminomas=0.1 (0.6), controls=1 (0), p
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- 2015
12. The expression of gene for beta catenin and p53 in meningioma
- Author
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Logara, Monika, Pećina-Šlaus, Nives, and Matulić, Maja
- Subjects
p53 ,signalni put Wnt ,Wnt signaling pathway ,PRIRODNE ZNANOSTI. Biologija ,beta-katenin ,NATURAL SCIENCES. Biology ,meningioma ,meninegeomi ,beta-catetin - Abstract
Meningeomi su primarni tumori središnjeg živčanog sustava. Beta-katenin je citoplazmatski protein kodiran genom CTNNB1. Sudjeluje u nastanku i održavanju međustaničnih veza i signalnom putu Wnt. Signalni put Wnt ima važnu ulogu tijekom embrionalnog razvojna, posebice razvoja središnjeg živčanog sustava. Osim stoga, neispravno funkcioniranje puta prijenosa signala Wnt odgovorno je za proces tumorigeneze. Neispravna akumulacija beta-katenina karakteristična je za različite tipove tumora. Postoje dokazi da su signalni putevi Wnt i p53 povezani te da divlji tip proteina p53 djeluje inhibitorno na Wnt signalizaciju. Željeli smo analizirati razinu izraženosti gena CTNNB1 (beta-katenin) i p53 u uzorcima meningeoma čovjeka te odrediti njihovu lokalizaciju u stanicama tumora. Također smo nastojali odrediti povezanost između ovih dvaju proteina i tako pokazati jesu li signalni putevi Wnt i p53 uključeni u nastanak meningeoma. Proteinske produkte gena CTNNB1 i p53 detektirali smo imunohistokemijom jer nam ova metoda omogućuje vizualizaciju antigena u preparatu što omogućuje samu vizualizaciju specifičnog proteina. Razinu ekspresije proteina beta-katenina i p53 odredili smo semikvantitativnom metodom tj. dodjeljivanjem znakova (+) Statističkom analizom razine ekspresije utvrdili smo da postoji inverzna korelacija izraženosti beta-katenina i p53 (P=-0,410; hi-kvadrat=0,002), što upućuje da gubitak ekspresije p53 dovodi do povišene razine beta-katenina i aktivacije signalnog puta Wnt. Meningiomas are primary tumors of the central nervous system. Beta-catenin is a cytoplasmic protein encoded by the CTNNB1 gene, it participates in the formation and maintenance of adherens junction and Wnt signaling pathway. Wnt signaling pathway plays an important role during embryonic development, specially in the development of the central nervous system. Disruption of Wnt signaling pathway may cause cells to favor process of tumorigenesis. Aberrant accumulation of beta-catenin is characteristic for different types of tumors. There is evidence that the Wnt signaling pathways and p53 are connected, and that wild-type p53 protein acts like inhibitor of Wnt signaling. In the present study we wanted to analyze the level of expression of beta-catenin and p53 in a sample of meningioma and determine their localization in tumor cells. We also sought to determine the association between these two proteins and explore whether Wnt signaling pathways and p53 are involved in the formation of meningiomas. Beta-catenin and p53 were detected by immunohistochemistry. The statistical analysis of expression levels showed that there is an inverse correlation between beta-catenin and p53 (P =-0.410; chi-square=0.002), which indicates that loss of p53 expression leads to aberrant acumulation of beta-catenin and activation of Wnt signaling pathway.
- Published
- 2015
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