Matches in SemOpenAlex for { <https://semopenalex.org/work/W2415694895> ?p ?o ?g. }
Showing items 1 to 83 of
83
with 100 items per page.
- W2415694895 abstract "BACKGROUND: Atypical teratoid rhabdoid tumor (ATRTs) constitute 20% of brain tumors in young children (<3 yrs of age) and is characterized by bi-allelic mutations of the INI-1 gene. The cell of origin in this tumor is not known and the mechanism by which INI-1 causes tumor is still not clear. Ubiquitin carboxyl-terminal hydrolase isoenzyme 1 (UCHL1), is an abundant neuronal de-ubiquitinating enzyme which acts as a tumor suppressor gene that is inactivated by promoter methylation / gene deletion in several cancers as well as an oncogene with overexpression in other cancers. The role of UCHL1 in brain tumors has not yet been studied. METHODS/RESULTS: We identified UCHL1 is silenced in ATRT cell lines (BT-12, BT-16) along with absent basal expression of p53 and NOXA by western blotting. UCHL1 silencing is mediated by promoter hyper-methylation (detected by using methylation specific PCR (MSP)); and pharmacologic de-methylation reactivated UCHL1 expression in these cell lines along with expression of p53 and NOXA. Ectopic expression of UCHL1 dramatically inhibited the growth of ATRT cell lines (using colony forming assay and MTT assay) and increased sensitivity to radiation. The growth inhibition was mediated by promoting tumor cell apoptosis resulting from activating the p53 tumor suppressor pathway. CONCLUSIONS: We have shown that UCHL1 is silenced in ATRT cell lines and acts as a tumor suppressor gene. We hypothesize that loss of p53 function due to silencing of UCHL1 drives tumor formation in the background of bi-allelic INI1 mutation in ATRT. We will further test this hypothesis using patient derived primary cell cultures and animal models (using genetically engineered mouse models INI1 +/- / UCHL1-/- mice)." @default.
- W2415694895 created "2016-06-24" @default.
- W2415694895 creator A5033184241 @default.
- W2415694895 creator A5042729959 @default.
- W2415694895 creator A5064701833 @default.
- W2415694895 creator A5070462994 @default.
- W2415694895 creator A5079044371 @default.
- W2415694895 creator A5082858469 @default.
- W2415694895 date "2015-11-01" @default.
- W2415694895 modified "2023-09-28" @default.
- W2415694895 title "PTPS-29UBIQUITIN CARBOXYL TERMINAL HYDROLASE-L1 (UCH-L1) IS A TUMOR SUPPRESSOR IN ATYPICAL TERATOID RHABDOID TUMORS (ATRTs)" @default.
- W2415694895 doi "https://doi.org/10.1093/neuonc/nov228.29" @default.
- W2415694895 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4639151" @default.
- W2415694895 hasPublicationYear "2015" @default.
- W2415694895 type Work @default.
- W2415694895 sameAs 2415694895 @default.
- W2415694895 citedByCount "0" @default.
- W2415694895 crossrefType "journal-article" @default.
- W2415694895 hasAuthorship W2415694895A5033184241 @default.
- W2415694895 hasAuthorship W2415694895A5042729959 @default.
- W2415694895 hasAuthorship W2415694895A5064701833 @default.
- W2415694895 hasAuthorship W2415694895A5070462994 @default.
- W2415694895 hasAuthorship W2415694895A5079044371 @default.
- W2415694895 hasAuthorship W2415694895A5082858469 @default.
- W2415694895 hasBestOaLocation W24156948951 @default.
- W2415694895 hasConcept C104317684 @default.
- W2415694895 hasConcept C119056186 @default.
- W2415694895 hasConcept C150194340 @default.
- W2415694895 hasConcept C153911025 @default.
- W2415694895 hasConcept C190727270 @default.
- W2415694895 hasConcept C2778264664 @default.
- W2415694895 hasConcept C2781018059 @default.
- W2415694895 hasConcept C29537977 @default.
- W2415694895 hasConcept C33288867 @default.
- W2415694895 hasConcept C502942594 @default.
- W2415694895 hasConcept C54355233 @default.
- W2415694895 hasConcept C555283112 @default.
- W2415694895 hasConcept C81885089 @default.
- W2415694895 hasConcept C86803240 @default.
- W2415694895 hasConcept C97037327 @default.
- W2415694895 hasConceptScore W2415694895C104317684 @default.
- W2415694895 hasConceptScore W2415694895C119056186 @default.
- W2415694895 hasConceptScore W2415694895C150194340 @default.
- W2415694895 hasConceptScore W2415694895C153911025 @default.
- W2415694895 hasConceptScore W2415694895C190727270 @default.
- W2415694895 hasConceptScore W2415694895C2778264664 @default.
- W2415694895 hasConceptScore W2415694895C2781018059 @default.
- W2415694895 hasConceptScore W2415694895C29537977 @default.
- W2415694895 hasConceptScore W2415694895C33288867 @default.
- W2415694895 hasConceptScore W2415694895C502942594 @default.
- W2415694895 hasConceptScore W2415694895C54355233 @default.
- W2415694895 hasConceptScore W2415694895C555283112 @default.
- W2415694895 hasConceptScore W2415694895C81885089 @default.
- W2415694895 hasConceptScore W2415694895C86803240 @default.
- W2415694895 hasConceptScore W2415694895C97037327 @default.
- W2415694895 hasLocation W24156948951 @default.
- W2415694895 hasLocation W24156948952 @default.
- W2415694895 hasOpenAccess W2415694895 @default.
- W2415694895 hasPrimaryLocation W24156948951 @default.
- W2415694895 hasRelatedWork W1533725726 @default.
- W2415694895 hasRelatedWork W1579585944 @default.
- W2415694895 hasRelatedWork W1603034668 @default.
- W2415694895 hasRelatedWork W2007228125 @default.
- W2415694895 hasRelatedWork W2008961465 @default.
- W2415694895 hasRelatedWork W2018787469 @default.
- W2415694895 hasRelatedWork W2040104122 @default.
- W2415694895 hasRelatedWork W2107334822 @default.
- W2415694895 hasRelatedWork W2118190502 @default.
- W2415694895 hasRelatedWork W2122844744 @default.
- W2415694895 hasRelatedWork W2145281459 @default.
- W2415694895 hasRelatedWork W2154930974 @default.
- W2415694895 hasRelatedWork W2161599883 @default.
- W2415694895 hasRelatedWork W2164811748 @default.
- W2415694895 hasRelatedWork W217147462 @default.
- W2415694895 hasRelatedWork W2319132174 @default.
- W2415694895 hasRelatedWork W2329951746 @default.
- W2415694895 hasRelatedWork W2526916257 @default.
- W2415694895 hasRelatedWork W2776683513 @default.
- W2415694895 hasRelatedWork W2912558220 @default.
- W2415694895 isParatext "false" @default.
- W2415694895 isRetracted "false" @default.
- W2415694895 magId "2415694895" @default.
- W2415694895 workType "article" @default.