formation-human-prostate-epithelium-using-tissue-recombination-rodent

Formation of Human Prostate Epithelium Using Tissue Recombination of Rodent Urogenital Sinus Mesenchyme and Human Stem Cells

Progress in prostate cancer research is severely  limited by the availability of human-derived and hormone-na&iuml;ve model systems,  which limit our ...

University of Chicago

Smooth muscle alpha-actin (SMA) is a cytoskeletal protein characteristic to vascular smooth muscle cells (VSMC), and it serves to facilitate cell contraction and migration. Bacterial lipopolysaccharide (LPS), a major mediator of septic shock secondary to infection, is known to directly affect VSMC. The objective of this study was to investigate the effect of LPS on the expression levels of SMA in VSMC.

Downregulation of smooth muscle alpha-actin expression by bacterial lipopolysaccharide.

Muscle lisse alpha-actine (SMA) est une caract&eacute;ristique de la prot&eacute;ine du cytosquelette de cellules du muscle lisse vasculaire (CMLV), et il sert &agrave; faciliter la migration et la contraction des cellules. Bact&eacute;rien lipopolysaccharides (LPS), un m&eacute;diateur important de secondaire &agrave; une infection, un choc septique est connu pour affecter directement les CMLV. L&#39;objectif de cette &eacute;tude &eacute;tait d&#39;&eacute;tudier l&#39;effet de LPS sur les niveaux d&#39;expression du SMA dans les CMLV.

Diminution d&#39;expression d&#39;alpha-actine muscle lisse par lipopolysaccharide bact&eacute;rien.

Alfa-actina del muscolo liscio (SMA) &egrave; una caratteristica di proteine citoscheletriche di cellule muscolari lisce vascolari (VSMC), e serve a facilitare la migrazione e la contrazione delle cellule. Batterica lipopolisaccaride (LPS), un importante mediatore di shock settico secondarie all&#39;infezione, &egrave; conosciuta per influenzare direttamente VSMC. L&#39;obiettivo di questo studio era di indagare l&#39;effetto dei LPS sui livelli di espressione di SMA in VSMC.

Downregulation di espressione alfa-actina muscolo liscio di lipopolisaccaride batterica.

Regulator of G protein signaling (RGS) proteins are united into a family by the presence of the homologous RGS domain that binds the alpha subunits of heterotrimeric G proteins and accelerates their GTPase activity. A member of this family, RGS3 regulates the signaling mediated by G(q) and G(i) proteins by binding the corresponding Galpha subunits. Here we show that RGS3 interacts with the novel partners Smad2, Smad3, and Smad4-the transcription factors that are activated through a transforming growth factor-beta (TGF-beta) receptor signaling. This interaction is mediated by the region of RGS3 outside of the RGS domain and by Smad's Mad homology 2 domain. Overexpression of RGS3 results in inhibition of Smad-mediated gene transcription. RGS3 does not affect TGF-beta-induced Smad phosphorylation, but it prevents heteromerization of Smad3 with Smad4, which is required for transcriptional activity of Smads. This translates to functional inhibition of TGF-beta-induced myofibroblast differentiation by RGS3. In conclusion, this study identifies a novel, noncanonical role of RGS3 in regulation of TGF-beta signaling through its interaction with Smads and interfering with Smad heteromerization.

Regulation of Smad-mediated gene transcription by RGS3.

R&eacute;gulateur de la prot&eacute;ine G, prot&eacute;ines (RGS) de signalisation sont Unis dans une famille par la pr&eacute;sence du domaine homologue RGS qui lie les sous-unit&eacute;s alpha des prot&eacute;ines G h&eacute;t&eacute;rotrim&eacute;riques et acc&eacute;l&egrave;re leur activit&eacute; GTPase. Un membre de cette famille, RGS3 r&eacute;gule la signalisation m&eacute;di&eacute; par les prot&eacute;ines G(q) et G(i) en liant les sous-unit&eacute;s Galpha correspondantes. Nous montrons ici que RGS3 interagit avec les nouveaux partenaires Smad2 et Smad3 Smad4-la transcription facteurs sont actionn&eacute;e au moyen d&#39;une signalisation de r&eacute;cepteur de facteur de croissance-b&ecirc;ta (TGF-b&ecirc;ta) transformant. Cette interaction est m&eacute;di&eacute;e par la r&eacute;gion de RGS3 en dehors du domaine RGS et par domaine d&#39;homologie Mad 2 de Smad. La surexpression de la RGS3 entra&icirc;ne l&#39;inhibition de la transcription du g&egrave;ne Smad-n&eacute;goci&eacute;e. RGS3 n&#39;affecte pas la phosphorylation Smad induite par TGF-b&ecirc;ta, mais il emp&ecirc;che heteromerization de Smad3 avec Smad4, qui est requis pour l&#39;activit&eacute; transcriptionnelle de SMAD. Cela se traduit par une inhibition fonctionnelle de diff&eacute;renciation induite par TGF-b&ecirc;ta myofibroblastes par RGS3. En conclusion, cette &eacute;tude identifie un r&ocirc;le novateur, non canonique de RGS3 dans le r&egrave;glement du TGF-b&ecirc;ta signalisation gr&acirc;ce &agrave; son interaction avec les Smad et interf&eacute;rant avec les Smad heteromerization.

R&eacute;gulation de la transcription de g&egrave;nes Smad par RGS3.

Regolatore della proteina G proteine (RGS) di segnalazione sono uniti in una famiglia dalla presenza del dominio RGS omologa che lega la subunit&agrave; alfa delle proteine G eterotrimerica e accelera la loro attivit&agrave; GTPasi. Un membro di questa famiglia, RGS3 regola la segnalazione mediata da proteine G(q) e G(i) legando la subunit&agrave; Galpha corrispondente. Qui vi mostriamo che RGS3 interagisce con il romanzo partner Smad2, Smad3 e Smad4, la trascrizione fattori che vengono attivati attraverso un recettore transforming growth factor-beta (TGF-beta) segnalazione. Questa interazione &egrave; mediata dalla regione di RGS3 di fuori del dominio RGS e dal dominio di omologia pazza 2 di Smad. Sovraespressione di RGS3 provoca l&#39;inibizione della trascrizione Smad-mediata del gene. RGS3 non pregiudica la fosforilazione indotta da TGF-beta Smad, ma previene l&#39;heteromerization di Smad3 con Smad4, che &egrave; necessaria per l&#39;attivit&agrave; trascrizionale di smad. Questo si traduce in inibizione funzionale di differenziazione myofibroblast TGF-beta-indotta da RGS3. In conclusione, questo studio identifica un ruolo canonica, romanzo di RGS3 nel regolamento del TGF-beta segnalazione attraverso l&#39;interazione con SMAD e interferire con heteromerization Smad.

Regolazione della trascrizione Smad-mediata del gene di RGS3.

Transforming growth factor-beta (TGF-beta) is a cytokine implicated in wound healing and in the pathogenesis of pulmonary fibrosis. TGF-beta stimulates myofibroblast differentiation characterized by expression of contractile smooth muscle (SM)-specific proteins such as SM-alpha-actin. In the present study, we examined the role of serum response factor (SRF) in the mechanism of TGF-beta-induced pulmonary myofibroblast differentiation of human lung fibroblasts (HLF). TGF-beta stimulated SM-alpha-actin expression in HLF, which paralleled with a profound induction of SRF expression and activity. Inhibition of SRF by the pharmacologic SRF inhibitor (CCG-1423), or via adenovirus-mediated transduction of SRF short hairpin RNA (shSRF), blocked the expression of both SRF and SM-alpha-actin in response to TGF-beta without affecting Smad-mediated signaling of TGF-beta. However, forced expression of SRF on its own did not promote SM-alpha-actin expression, whereas expression of the constitutively transactivated SRF fusion protein (SRF-VP16) was sufficient to induce SM-alpha-actin expression, suggesting that both expression and transactivation of SRF are important. Activation of protein kinase A (PKA) by forskolin or iloprost resulted in a significant inhibition of SM-alpha-actin expression induced by TGF-beta, and this was associated with inhibition of both SRF expression and activity, but not of Smad-mediated gene transcription. In summary, this is the first direct demonstration that TGF-beta-induced pulmonary myofibroblast differentiation is mediated by SRF, and that inhibition of myofibroblast differentiation by PKA occurs through down-regulation of SRF expression levels and SRF activity, independent of Smad signaling.

Critical role of serum response factor in pulmonary myofibroblast differentiation induced by TGF-beta.

Transforming growth factor-beta (TGF-b&ecirc;ta) est une cytokine impliqu&eacute;e dans la cicatrisation des plaies et dans la pathogen&egrave;se de la fibrose pulmonaire. TGF-b&ecirc;ta stimule la diff&eacute;renciation des myofibroblastes caract&eacute;ris&eacute;e par l&#39;expression du muscle contractile (SM)-prot&eacute;ines sp&eacute;cifiques tels que SM-alpha-actine. Dans la pr&eacute;sente &eacute;tude, nous avons examin&eacute; le r&ocirc;le du facteur de r&eacute;ponse s&eacute;rique (SRF) dans le m&eacute;canisme de la diff&eacute;renciation des myofibroblastes pulmonaire induite par le TGF-b&ecirc;ta de fibroblastes pulmonaires humaines (HLF). TGF-b&ecirc;ta stimul&eacute;e expression SM-alpha-actine dans HLF, qui en parall&egrave;le avec une profonde induction de l&#39;expression de la SRF et l&#39;activit&eacute;. L&#39;inhibition de la SRF par l&#39;inhibiteur pharmacologique de la SRF (GCC-1423), ou par l&#39;interm&eacute;diaire de transduction ad&eacute;novirale d&#39;&eacute;pingle &agrave; cheveux court SRF RNA (shSRF), bloqu&eacute; l&#39;expression des r&eacute;sultats strat&eacute;giques et d&#39;alpha-actine en r&eacute;ponse &agrave; TGF-beta sans signalisation affectant m&eacute;di&eacute;e par Smad du TGF-beta. Toutefois, expression forc&eacute;e de SRF &agrave; elle seule n&#39;encourageaient pas expression SM-alpha-actine, consid&eacute;rant que l&#39;expression de la prot&eacute;ine de fusion constitutivement transactivated SRF (SRF-VP16) &eacute;tait suffisante pour induire l&#39;expression de SM-alpha-actine, sugg&eacute;rant que l&#39;expression et transactivation de CRS sont importants. Activation de la prot&eacute;ine kinase A (PKA) par la forskoline ou iloprost a entra&icirc;n&eacute; une inhibition significative de l&#39;expression de SM-alpha-actine induite par le TGF-b&ecirc;ta, et ceci a &eacute;t&eacute; associ&eacute; &agrave; l&#39;inhibition de l&#39;expression de la SRF et l&#39;activit&eacute;, mais pas de transcription des g&egrave;nes Smad. En r&eacute;sum&eacute;, c&#39;est la premi&egrave;re d&eacute;monstration directe que diff&eacute;renciation myofibroblastes pulmonaire induite par le TGF-b&ecirc;ta est m&eacute;di&eacute;e par les CRS, et que l&#39;inhibition de la diff&eacute;renciation des myofibroblastes de PKA s&#39;effectue via la r&eacute;gulation &agrave; la baisse des niveaux d&#39;expression de SRF et activit&eacute; SRF, ind&eacute;pendante de la signalisation des Smad.

R&ocirc;le essentiel de la r&eacute;ponse de s&eacute;rum facteur de diff&eacute;renciation des myofibroblastes pulmonaire induite par le TGF-b&ecirc;ta.

Transforming growth factor-beta (TGF-beta) &egrave; una citochina coinvolta nella guarigione delle ferite e nella patogenesi della fibrosi polmonare. TGF-beta stimola la differenziazione myofibroblast caratterizzata dall&#39;espressione di muscolo liscio contrattile (SM)-proteine specifiche come SM-alfa-actina. Nel presente studio, abbiamo esaminato il ruolo del fattore di risposta del siero (SRF) nel meccanismo di differenziazione myofibroblast polmonare indotta da TGF-beta di fibroblasti di polmone umano (HLF). TGF-beta stimolata espressione SM-alfa-actina in HLF, che parallelo con una profonda induzione dell&#39;espressione di SRF e attivit&agrave;. Inibizione della SRF di inibitore SRF farmacologica (CCG-1423), o tramite trasduzione dell&#39;adenovirus-mediata del tornante breve SRF RNA (shSRF), bloccato l&#39;espressione di SRF e SM-alfa-actina in risposta al TGF-beta senza che interessano Smad-mediata segnalazione di TGF-beta. Tuttavia, espressione forzata di SRF in proprio non ha fatto promuovere espressione SM-alfa-actina, considerando che l&#39;espressione della proteina di fusione di SRF (SRF-VP16) costitutivamente transactivated era sufficiente per indurre l&#39;espressione di SM-alfa-actina, suggerendo che sia espressione e transactivation di SRF sono importanti. Attivazione della chinasi di proteina A (PKA) di forskolina o iloprost ha portato a una significativa inibizione dell&#39;espressione di SM-alfa-actina indotti dal TGF-beta, e questa &egrave; stata associata con l&#39;inibizione dell&#39;espressione di SRF e l&#39;attivit&agrave;, ma non della trascrizione Smad-mediata del gene. In sintesi, questa &egrave; la prima dimostrazione diretta che differenziazione myofibroblast polmonare indotta da TGF-beta &egrave; mediata da SRF, e che l&#39;inibizione della differenziazione myofibroblast dal PKA avviene attraverso la down-regulation dei livelli di espressione di SRF e attivit&agrave; SRF, indipendente di segnalazione Smad.

Ruolo critico di risposta del siero di fattore nella differenziazione myofibroblast polmonare indotta da TGF-beta.

Il rabdomiosarcoma (RMS) &egrave; il pi&ugrave; comune sarcoma dei tessuti molli nei bambini. Attuali strategie di trattamento non cura la maggior parte dei bambini con malattie ricorrenti o ad alto rischio, la necessit&agrave; di nuovi approcci terapeutici alla base. L&#39;acido retinoico ha dimostrato di indurre la differenziazione in una variet&agrave; di cellule tra cui neuroblasti e mioblasti scheletrici. Nella cornice della minimal residual disease, acido retinoico migliora la sopravvivenza nel neuroblastoma, un altro tumore infantile scarsamente differenziati. Se un tale approccio &egrave; utile per il rabdomiosarcoma &egrave; non ancora stato studiato. Diversi studi in vitro hanno dimostrato un effetto apprezzabile di acido retinoico su umano proliferazione di RMS cellulare e la differenziazione.

L&#39;acido retinoico non riesce a indurre l&#39;arresto del ciclo cellulare con differenziazione miogena nel rabdomiosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Current treatment strategies do not cure most children with recurrent or high-risk disease, underlying the need for novel therapeutic approaches. Retinoic acid has been shown to induce differentiation in a variety of cells including skeletal myoblasts and neuroblasts. In the setting of minimal residual disease, retinoic acid improves survival in neuroblastoma, another poorly differentiated childhood tumor. Whether such an approach is useful for rhabdomyosarcoma has not yet been investigated. Several in vitro studies have demonstrated an appreciable effect of retinoic acid on human RMS cellular proliferation and differentiation.

Retinoic acid fails to induce cell cycle arrest with myogenic differentiation in rhabdomyosarcoma.

Rhabdomyosarcome (RMS) est la plus courant sarcome des tissus mous chez les enfants. Les strat&eacute;gies de traitement actuelles ne gu&eacute;rissent pas la plupart des enfants atteints de maladies r&eacute;currentes ou &agrave; haut risque, qui sous-tendent la n&eacute;cessit&eacute; de nouvelles approches th&eacute;rapeutiques. L&#39;acide r&eacute;tino&iuml;que a &eacute;t&eacute; d&eacute;montr&eacute; pour induire la diff&eacute;renciation dans une vari&eacute;t&eacute; de cellules, y compris les neuroblastes et les myoblastes squelettiques. Dans le cadre de la maladie r&eacute;siduelle, l&#39;acide r&eacute;tino&iuml;que am&eacute;liore la survie dans le neuroblastome, une autre tumeur peu diff&eacute;renci&eacute; de l&#39;enfance. Si cette approche est utile pour Rhabdomyosarcome n&#39;a pas encore &eacute;t&eacute; examin&eacute;e. Plusieurs &eacute;tudes in vitro ont d&eacute;montr&eacute; un effet de l&#39;acide r&eacute;tino&iuml;que sur humain prolif&eacute;ration de RMS cellulaire et la diff&eacute;renciation.

L&#39;acide r&eacute;tino&iuml;que ne parvient pas &agrave; provoquer l&#39;arr&ecirc;t du cycle cellulaire avec la diff&eacute;renciation myog&eacute;nique dans Rhabdomyosarcome.

In the adult human prostate CD133 expression is thought to mark rare prostate epithelial stem cells and malignant tumor stem/initiating cells. Such putative stem cell populations are thought to proliferate slowly, but possess unlimited proliferative potential. Based on this, we hypothesized that CD133(pos) prostate cancer cells proliferate slower than CD133(neg) cells.

Growth kinetics of CD133-positive prostate cancer cells.

Dans l&#39;expression de CD133 la prostate humaine adulte est pens&eacute;e pour marquer les cellules souches &eacute;pith&eacute;liales rares la prostate et les cellules de tige/initier une tumeur maligne. On pense que ces populations putatif des cellules souches prolif&egrave;rent lentement, mais poss&egrave;dent un potentiel prolif&eacute;ratif illimit&eacute;. Sur cette base, nous avons suppos&eacute; que CD133(pos) cellules prostatiques canc&eacute;reuses prolif&egrave;rent plus lentement que les cellules CD133(neg).

Cin&eacute;tique de croissance des cellules de cancer de la prostate CD133-positives.

Nell&#39;espressione CD133 prostatico umano adulto &egrave; pensato per contrassegnare rare cellule staminali epiteliali della prostata e il tumore maligno delle cellule staminali/avvio. Pensiero che tali popolazioni putative sulle cellule staminali proliferare lentamente, ma possiedono un potenziale proliferativo illimitato. Su questa base, abbiamo ipotizzato che CD133(pos) le cellule tumorali della prostata pi&ugrave; lento del CD133(neg) cellule proliferano.

Cinetica di crescita delle cellule tumorali della prostata CD133-positivo.

Despite advances in detection and therapy, castration-resistant prostate cancer continues to be a major clinical problem. The aberrant activity of stem cell pathways, and their regulation by the Androgen Receptor (AR), has the potential to provide insight into novel mechanisms and pathways to prevent and treat advanced, castrate-resistant prostate cancers. To this end, we investigated the role of the embryonic stem cell regulator Sox2 [SRY (sex determining region Y)-box 2] in normal and malignant prostate epithelial cells. In the normal prostate, Sox2 is expressed in a portion of basal epithelial cells. Prostate tumors were either Sox2-positive or Sox2-negative, with the percentage of Sox2-positive tumors increasing with Gleason Score and metastases. In the castration-resistant prostate cancer cell line CWR-R1, endogenous expression of Sox2 was repressed by AR signaling, and AR chromatin-IP shows that AR binds the enhancer element within the Sox2 promoter. Likewise, in normal prostate epithelial cells and human embryonic stem cells, increased AR signaling also decreases Sox2 expression. Resistance to the anti-androgen MDV3100 results in a marked increase in Sox2 expression within three prostate cancer cell lines, and in the castration-sensitive LAPC-4 prostate cancer cell line ectopic expression of Sox2 was sufficient to promote castration-resistant tumor formation. Loss of Sox2 expression in the castration-resistant CWR-R1 prostate cancer cell line inhibited cell growth. Up-regulation of Sox2 was not associated with increased CD133 expression but was associated with increased FGF5 (Fibroblast Growth Factor 5) expression. These data propose a model of elevated Sox2 expression due to loss of AR-mediated repression during castration, and consequent castration-resistance via mechanisms not involving induction of canonical embryonic stem cell pathways.

Sox2 is an androgen receptor-repressed gene that promotes castration-resistant prostate cancer.

Malgr&eacute; les progr&egrave;s r&eacute;alis&eacute;s dans la d&eacute;tection et le traitement, cancer de la prostate r&eacute;sistant &agrave; la castration continue d&#39;&ecirc;tre un probl&egrave;me clinique majeur. L&#39;activit&eacute; aberrante des voies de cellules souches et leur r&eacute;gulation par le r&eacute;cepteur aux androg&egrave;nes (AR), a le potentiel pour donner un aper&ccedil;u de nouveaux m&eacute;canismes et voies pour pr&eacute;venir et traiter les cancers de la prostate avanc&eacute;s, r&eacute;sistants &agrave; la castration. &Agrave; cette fin, nous avons &eacute;tudi&eacute; le r&ocirc;le de l&#39;autorit&eacute; de r&eacute;gulation des cellules souches embryonnaires Sox2 [SRY (sex d&eacute;terminant r&eacute;gion Y)-bo&icirc;te 2] dans les cellules &eacute;pith&eacute;liales prostatiques normaux et malins. Dans la prostate normale, Sox2 est exprim&eacute;e dans une partie des cellules &eacute;pith&eacute;liales basales. Tumeurs de la prostate ont &eacute;t&eacute; soit Sox2-positif ou n&eacute;gatif Sox2, avec le pourcentage de tumeurs Sox2 positifs augmente avec un Score de Gleason et m&eacute;tastases. Dans la lign&eacute;e cellulaire de cancer de la prostate r&eacute;sistant &agrave; la castration LRS-R1, expression endog&egrave;ne de Sox2 &eacute;tait r&eacute;prim&eacute;e par AR de signalisation, et AR la chromatine-IP montre que AR lie l&#39;&eacute;l&eacute;ment enhancer dans le promoteur Sox2. De m&ecirc;me, dans les cellules &eacute;pith&eacute;liales prostatiques normales et les cellules souches embryonnaires humaines, accrue de signalisation AR diminue &eacute;galement Sox2 expression. R&eacute;sistance &agrave; la MDV3100 anti-androg&egrave;ne se traduit par une augmentation marqu&eacute;e de Sox2 expression au sein de trois lign&eacute;es cellulaires de cancer de la prostate, et dans la castration sensibles LAPC-4 expression ectopique de ligne cell cancer de la prostate de Sox2 serait suffisante pour favoriser la formation de tumeurs r&eacute;sistant &agrave; la castration. Perte d&#39;expression Sox2 dans la lign&eacute;e de cellules de cancer de la prostate LRS-R1 r&eacute;sistante &agrave; la castration inhibe la croissance cellulaire. R&eacute;gulation de Sox2 n&#39;&eacute;tait pas associ&eacute;e &agrave; une expression accrue CD133 mais a &eacute;t&eacute; associ&eacute;e &agrave; une augmentation FGF5 expression (Fibroblast Growth Factor 5). Ces donn&eacute;es proposent un mod&egrave;le d&#39;expression de Sox2 &eacute;lev&eacute;e en raison de la perte de r&eacute;pression m&eacute;di&eacute;e par AR au cours de la castration et cons&eacute;quente castration-r&eacute;sistance par l&#39;interm&eacute;diaire de m&eacute;canismes n&#39;impliquant ne pas l&#39;induction des voies canoniques les cellules souches embryonnaires.

Sox2 est un g&egrave;ne de r&eacute;prim&eacute;s r&eacute;cepteurs androg&egrave;nes qui favorise le cancer de la prostate r&eacute;sistant &agrave; la castration.

Nonostante i progressi della terapia e rilevazione, il cancro alla prostata resistente a castrazione continua ad essere un grave problema clinico. L&#39;attivit&agrave; aberrante di cellule staminali percorsi e loro regolamento dal recettore degli androgeni (AR), ha il potenziale per fornire nuovi meccanismi e percorsi per prevenire e trattare i tumori della prostata avanzati, castrate-resistente. A tal fine, abbiamo studiato il ruolo del regolatore delle cellule staminali embrionali Sox2 [SRY (determinazione regione Y del sesso)-casella 2] normale e maligna delle cellule epiteliali della prostata. Nella prostata normale, Sox2 &egrave; espressa in una porzione di cellule epiteliali basali. I tumori della prostata sono stati Sox2-positivo o negativo Sox2, con la percentuale di tumori positivi Sox2 aumentando con il punteggio di Gleason e metastasi. La linea cellulare di cancro alla prostata resistente a castrazione CWR-R1, espressione endogena di Sox2 fu repressa da AR di segnalazione, e AR cromatina-IP dimostra che AR associa l&#39;elemento enhancer all&#39;interno del promotore Sox2. Similarmente, in normali cellule epiteliali prostatiche e cellule staminali embrionali umane, anche maggiore AR signaling diminuisce Sox2 espressione. Resistenza al MDV3100 antiandrogeni si traduce in un marcato aumento in Sox2 espressione all&#39;interno di tre linee di cellule di cancro alla prostata, e la castrazione sensibili LAPC-4 il cancro alla prostata cella linea l&#39;espressione ectopica di Sox2 era sufficiente per promuovere la formazione di tumori castrazione-resistente. Perdita di Sox2 espressione nella linea cellulare di cancro alla prostata CWR-R1 castrazione-resistente ha inibito la crescita cellulare. Up-regolazione di Sox2 non era associato con aumentata espressione di CD133 ma &egrave; stato associato con aumento FGF5 (Fibroblast Growth Factor 5) espressione. Questi dati di proporre un modello di espressione di Sox2 elevati a causa della perdita di AR-mediata repressione durante la castrazione e la conseguente castrazione-resistenza attraverso meccanismi che non coinvolgono induzione di percorsi canonici delle cellule staminali embrionali.

Steven Kregel

Committee on Cancer Biology

University of Chicago

Formation of Human Prostate Epithelium Using Tissue Recombination of Rodent Urogenital Sinus Mesenchyme and Human Stem Cells

Steven Kregel

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Committee on Cancer Biology

University of Chicago

Formation of Human Prostate Epithelium Using Tissue Recombination of Rodent Urogenital Sinus Mesenchyme and Human Stem Cells

Committee on Cancer Biology