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Statements

Subject Item
n2:RIV%2F00216208%3A11120%2F13%3A43907407%21RIV14-MZ0-11120___
rdf:type
skos:Concept n11:Vysledek
dcterms:description
Metastasized malignant melanoma has a poor prognosis because of its intrinsic resistance to chemotherapy and radiotherapy. The central role in the melanoma transcriptional network has the transcription factor MITF (microphthalmia-associated transcription factor). It has been shown recently that the expression of MITF and some of its target genes require the SWI/SNF chromatin remodeling complex. Here we demonstrate that survival of melanoma cells requires functional SWI/SNF complex not only by supporting expression of MITF and its targets and but also by activating expression of prosurvival proteins not directly regulated by MITF. Microarray analysis revealed that besides the MITF-driven genes, expression of proteins like osteopontin, IGF1, TGF beta 2 and survivin, the factors known to be generally associated with progression of tumors and the antiapoptotic properties, were reduced in acute BRG1-depleted 501mel cells. Western blots and RT-PCR confirmed the microarray findings. These proteins have been verified to be expressed independently of MITF, because MITF depletion did not impair their expression. Because these genes are not regulated by MITF, the data suggests that loss of BRG1-based SWI/SNF complexes negatively affects survival pathways beyond the MITF cascade. Immunohistochemistry showed high expression of both BRM and BRG1 in primary melanomas. Exogenous CDK2, osteopontin, or IGF1 each alone partly relieved the block of proliferation imposed by BRG1 depletion, implicating that more factors, besides the MITF target genes, are involved in melanoma cell survival. Together these results demonstrate an essential role of SWI/SNF for the expression of MITF-dependent and MITF-independent prosurvival factors in melanoma cells and suggest that SWI/SNF may be a potential and effective target in melanoma therapy. Metastasized malignant melanoma has a poor prognosis because of its intrinsic resistance to chemotherapy and radiotherapy. The central role in the melanoma transcriptional network has the transcription factor MITF (microphthalmia-associated transcription factor). It has been shown recently that the expression of MITF and some of its target genes require the SWI/SNF chromatin remodeling complex. Here we demonstrate that survival of melanoma cells requires functional SWI/SNF complex not only by supporting expression of MITF and its targets and but also by activating expression of prosurvival proteins not directly regulated by MITF. Microarray analysis revealed that besides the MITF-driven genes, expression of proteins like osteopontin, IGF1, TGF beta 2 and survivin, the factors known to be generally associated with progression of tumors and the antiapoptotic properties, were reduced in acute BRG1-depleted 501mel cells. Western blots and RT-PCR confirmed the microarray findings. These proteins have been verified to be expressed independently of MITF, because MITF depletion did not impair their expression. Because these genes are not regulated by MITF, the data suggests that loss of BRG1-based SWI/SNF complexes negatively affects survival pathways beyond the MITF cascade. Immunohistochemistry showed high expression of both BRM and BRG1 in primary melanomas. Exogenous CDK2, osteopontin, or IGF1 each alone partly relieved the block of proliferation imposed by BRG1 depletion, implicating that more factors, besides the MITF target genes, are involved in melanoma cell survival. Together these results demonstrate an essential role of SWI/SNF for the expression of MITF-dependent and MITF-independent prosurvival factors in melanoma cells and suggest that SWI/SNF may be a potential and effective target in melanoma therapy.
dcterms:title
MITF-Independent Pro-Survival Role of BRG1-Containing SWI/SNF Complex in Melanoma Cells MITF-Independent Pro-Survival Role of BRG1-Containing SWI/SNF Complex in Melanoma Cells
skos:prefLabel
MITF-Independent Pro-Survival Role of BRG1-Containing SWI/SNF Complex in Melanoma Cells MITF-Independent Pro-Survival Role of BRG1-Containing SWI/SNF Complex in Melanoma Cells
skos:notation
RIV/00216208:11120/13:43907407!RIV14-MZ0-11120___
n11:predkladatel
n12:orjk%3A11120
n3:aktivita
n13:S n13:P
n3:aktivity
P(NT11229), S
n3:cisloPeriodika
1
n3:dodaniDat
n9:2014
n3:domaciTvurceVysledku
n19:1315145
n3:druhVysledku
n14:J
n3:duvernostUdaju
n4:S
n3:entitaPredkladatele
n5:predkladatel
n3:idSjednocenehoVysledku
88557
n3:idVysledku
RIV/00216208:11120/13:43907407
n3:jazykVysledku
n17:eng
n3:klicovaSlova
master regulator; cutaneous melanoma; increased expression; lung-cancer; transcription factor MITF; chromatin remodeling complexes
n3:klicoveSlovo
n7:lung-cancer n7:transcription%20factor%20MITF n7:increased%20expression n7:master%20regulator n7:cutaneous%20melanoma n7:chromatin%20remodeling%20complexes
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[F6D721D46536]
n3:nazevZdroje
PLoS One
n3:obor
n10:FD
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
5
n3:projekt
n15:NT11229
n3:rokUplatneniVysledku
n9:2013
n3:svazekPeriodika
8
n3:tvurceVysledku
Ondrušová, Lubica
n3:wos
000313738900040
s:issn
1932-6203
s:numberOfPages
10
n16:organizacniJednotka
11120